Acta path. et microhiol. scandinav. 64, 31-49, 1965.

~~
)

I
j

The Department of Pathological Anatomy, University of Turlm, Turku, Finland.

(Head: Prof. Osmo Jiirvi, l\I.D.)

THE TWO HISTOLOGICAL MAIN TYPES

OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED
INTESTINAL-TYPE CARCINOMA
An Attempt at a Histo-Clinical Classification

By
PEKKA LAURE!\'1
Received 19.i.65

The histological classification of gastric carcinomas is difficult as

these tumours appear to he very varying structurally. This has led to
considerable confusion in the histological terminology of gastric cancer.
Moreover, the descriptive histological types such as adenocarcinoma,
papillary, solid, scirrhous and colloid carcinoma appear to show a
fairly poor correlation with the other features of the disease. The
significance of histological classification was denied completely by
Slont (1953) and Ackaman & del Regalo (1962) who advanced the
view that the histological structure of gastric carcinoma shows arbi-
trary 'differences in the various parts of the tumour. But the necessity
of defining the histological basic types associated with the other fea-
tures of gastric carcinomas has also been emphasized (Schindler 1941,
Hamper[ 1956, conclusions of the Symposium on the GcO[Jraphical
Pallwlogy of Gastro-intestinal Cancer 1961).
As gastric carcinoma obviously may he preceded by different patho-
logical changes in the mucosa, and as the gastric mucosa is composed
of many different cell types, there is reason to assume that the group
of gastric carcinomas also includes forms with specific structural dif-
ferences. In tlwir study of this point .Jiirvi & Lauren (1 951) established
that the histological structure of gastric carcinoma often displays fea-
tures characteristic of intestinal mucosa and claimed that in at least
50 per cent of the cases gastric carcinomas arise from intestinal meta-
plasias in the stomach. On the basis of corresponding observations
(Mulligan & Rember 1954, Morson 1955, 1962, Wattenberg 1059, llen-
schcn 1960) the name "intestinal-type gastric carcinoma" has become
increasingly used in the literature.
The present study-a preliminary report of the results has heen

1
The work was supported by the Damon Runyon Memorial Fund.
 32

given ea rlier (Lauren 1964) - tri ed to es tablish whether intestinal-type

gas tric ca rcinoma co nstitutes a uniform stru c tural a nd pathogenetic
entity which can be differ entiated distinctly from other gastric car-
cinomas and, wh eth e r other hi stologic carcinoma groups with specific
properties ex ist.

Specimen s t a ken at o per a ti o n for gas tri c ca r cin om a on 1344 patients were studi ed
in th e Departme nt o f Pathological Anatomy, U niver s ity of Turlm in 1945- 1964. Th e
s pecime n s were fixed in formalin and studi ed in sec tions st a in ed by th e h acm a-
toxy l in -van Gieson technique. In addition, 309 cases were studied by seve ral o th er
methods. Bes ides th e h ae mat oxylin-va n Gieson technique, H eid cnh a in's aza n techni -
qu e was u sed as a general st a ining method sin ce it di splays m o r e clearly the bru sh
border, Pancth's cell s, a nd mucus. For mucu s stainin g, p eriodi c ac id Schiff (PAS)
techniqu e a ft er diastase tr ea tm ent was u sed; for th e dem on stra ti on of ac id mucu s,
a lso a lei a n blu e, ald ehyde fu ch sin a nd mu cicarmin e ; and for th e dem o n strati o n of
n eu tral mucu s, Best's carmin e a ft er di as tase tr ea tment w as u sed. Both th e Masso n-
H a mp erl a nd th e Bodian reactions we1·e u sed t o brin g o ut th e ent er oc hr omaffin
cell s.

The tumours were first class ifi ed into groups according to th eir
morphologic characteristics. Th e sa m e tumour often revealed several
of these sub-types which corresponded to th e descriptive hi stological
typ es in general us e. Finally, when th e sub-types that were found to
b e mutuall y transform able were co mbined , two main types could b e
discerned. In the se ri es 53 p er cent of the tumours ( 715 cases) w er e
found to belong to a main type consisting mainly of tumours of adeno-
matous structure. The name intes tinal-type gastric ca rcinoma a lready
m entioned above was u sed for this group b ecau se all tumours of thi s
structural typ e occur as primary co lon cance r as well. Another main typ e,
33 pe r cent ( 441 cases ), differed from th e intes tinal type both in
gener a l and cellular s tru cture and in mod e of sec retion. Th ese tumours
were called diffus e gastric carcinoma in view of th eir mann er of
g rowth. In th e r emaining 14 per cent ( 188 cases), the structure of the
carcinom a differed from both main types. This group- a more de-
tailed stmctural analysis is outside the scope of the present study- is
h eterogen eou s in composition. Belonging to thi s group arc ca rcinomas
of intes tina l a nd diffu se typ e th e classification of which invol ves som e
uncertainty becau se of their atypical or poorly differentiated structure.
A "colliding carcinoma" ( Oola & Tanaka 1952) of obviously multi-
centric origin was encountered in a few cases . Finally, the group in-
cludes tumours of a specific, individual structural typ e including rare
acinar carcinomas provided with excretory ducts which have been re-
ported ea rlier (Jarvi & Lauren 1964).
Neither of th e two m ain typ es has a direct counterpart among the
classical descriptive types of gastric carcinoma. Intestinal-type ca r-
cinomas include, besides pure a denoca rcinomas, forms which occur as
their variants and can differ considerably from one another in their
gen eral stru cture, but which show simila rities both of cellulat· struc-
ture and mod e of g rowth. Such sub-types are papillary ca rcinom as and
 33

some solid, scirrhous and colloid carcinomas. To the diffuse type be-
long primarily the so-called undifferentiated carcinomas and some of
the carcinomas earlier diagnosed as solid, scirrhous or colloid. They
can also display a slight tendency to form glandular structure.
An endeavour was made to establish how far these two histological
main types differ mutually in 1) cell structure, with SJWcial reference
to the presence of intestinal epithelial characteristics, 2) mode of secre-
tion and the histochemical properties of the secreta, 3) mode of growth,
and 4) clinical features of the disease.

DIFFEHENTIAL DIAGNOSIS OF INTESTINAL-TYPE

AND DIFFUSE GASTRIC CARCINOMA

In the classification of the tumours attention was paid to the struc-

tural characteristics enumerated below. They were of different degree
in different tumours, and occasionally some of these properties failed
to emerge at all.
General slmclure. Distinct, usually large glandular lumina were
typical of intestinal-type carcinoma (Figs. 1 and 3). They were often
accompanied by papillary fold formation or solid components, hut the
glandular structure was rarely completely absent. \Vhen it was, the
solid carcinomatous tissue was seen to form distinct epithelial tracts.
In diffuse carcinomas cells were found to he scattered either as solitary
cells or as small clusters of cells (Figs. 2 and 4). Glandular lumina
were rarely seen, when present they were generally quite small and of
indistinct shape, easy to distinguish from the well-defined lumina of
intestinal-type carcinoma (Fig. fi). Diffuse carcinoma, occasionally of
a more cellular appearance, might form appan•ntly solid masses; hut
even in these cases the cells seemed to he only loosely attached to one
another forming no distinct epithelium-like cords.
Cell structure. The cells of intestinal-type carcinoma were consider-
ably larger, more clearly defined, and morphologically more variable
than the cells seen in diffuse carcinoma. In diffuse carcinoma, the
~yto)llasm was indistinctly defined and fragile, and the shape of the
cells more uniform. They were often difficult to recognize as epithelial
cells when they appeared as solitary cells or in small clusters.
A similar difference was seen in the structure of the nuclei. In the
intestinal-type carcinomas the nuclei were large, of variable shape,
hyperchromatic, often showing mitotic figures. The nuclei were smaller
in diffuse carcinomas, smooth-edged, more regular in form, evenly or
only faintly hyperchromatic, often however, pyknotic. Mitotic figures
Were generally fairly difficult to t>stablish.
The cells of intestinal-type carcinoma which lined the glandular
lumina were as a rule fairly well polarized columnar cells (Fig. 3).
The apical surface of the cells continued unbroken from one cell to
another. It was possible to demonstrate a well-developed brush border

3 ACTA PATH. 64, 1

 35
in 83 per cent ( 146/176 cases) of all intestinal-type carcinomas and in
92 per cent (146/15!)) of the intestinal-type carcinomas forming glan-
dular structure. The cells lining the lumina which occasionally were
encountered in diffuse carcinomas were unpolarized, randomly grouped
and the apical surface from cell to cell was of a wavy form (Fig. 5).
Surface differentiation of brush border type was demonstrated in 11
per cent ( 10/!)4) of all and in 48 per cent (1 0/21) of diffuse carcinomas
forming glandular structure. The formation, however, was g('JH'rally
more uneven and the hristlt•s were more sparse than in the brush
hor9er seen in the cells of intestinal-type carcinomas.
Secretion. Eighteen per cent ( 30/171) of the intestinal-type carci-
nomas showed no cells containing secretory products. In diffuse car-
cinomas all the tumours studied by mucus staining methods displayed
secreting cells. Most of the secreting intestinal-type carcinomas ( 61 per
cent, 86/141) had only few secreting cells among the protoplasmatic
cells (Fig. 6). Ninety per cent (79/88) of the diffuse carcinomas dis-
played secretion over extensive areas in nearly all of the tumour cells
(Fig. 7). In the intestinal-type carcinomas secretion almost always
formed a distinctly defined theca in the cytoplasm; in diffuse carci-
nomas it appeared always to be evenly distributed in the cytoplasm.
The extracellular secreted mucus was located chiefly in the glandular
lumina in intestinal-type carcinomas and dispersed in the stroma in
diffuse carcinomas. Extracellular mucus was missing completely in
23 per cent (:"19/171) of the intestinal-type and in 6il per cent ( 59/94)
of the diffuse carcinomas.
Colloid carcinoma arose from carcinomas of intestinal as well as of
diffuse type. This was sren in 11 per crnt ( 1!)/171) of the intestinal-
type and in 21 per cent (20/9-1) of the diffuse carcinomas. The structure
of the colloid carcinoma differed in these two carcinoma types. Colloid
carcinoma of intestinal type mostly arose secondarily from ad(•no-
carcinoma when the glandular lumina were dilated and split hy profuse
mucus (Fig. 8). It originated more rarely from the transformation of
the crlls of a solid carcinoma into mucus-filled signet ring cells (pri-
mary colloid carcinoma of the colon, Raiford 1932). Colloid carcinoma
of diffuse type arose from mucus masses which accumulated around
isolat('<l cells or loose cell clust('rs (Fig. 9). In some part of the tumour

Fig.t-2.
Fig. 1. General picture of intestinal-type adenopapillary carcinoma with necroses
in the laq(e glands. The mucosa shows atrophic-hyperplastic gastritis with
,, intestinal metaplasia. Hacmatoxylin-van Gieson staining. X 25.
F 1Y· 2. General pidure of diffuse carcinoma. The scanty, dispcrst•d tumour tissue is
distinguishable with difficulty in the submucosa. The tumour tissue spreads
profusely to the deeper parts of the mucosa. Large folds formed by the gastric
surface epithelium arc seen in the mucosa, hut no intestinal metaplasia. The
gastritic changes in the parts of the mucosa free from carcinoma are slight.
Haematoxylin-van Gieson staining. X 25.

3•
 36

Fig. 3- 4.
Fig. 3. Gl a nd s of int es tin al -ty p e ca r cin om a . Th e ce ll s a r e fairl y w ell p ol a r ized hi gh
column a r cell s. In thi s area, which i s di sta nt fr om th e ulc er a ti on , th e s tr o m a
di s pl ays pr ofu se infl a mm a t o1·y cell infiltra ti on chi e fl y b y po lym o rph o nucl ca i'
l cu cocy t cs. H ac m a t oxy lin -mu c ica rmin c s t a inin g. X 160.
Fig. 4. A n ea rl y so lid m ass o f l oose ly gr oup ed ce ll s in diffu se ca r cin om a whi ch d ocs
n o l f orm a n y di s tin ct epith elium -lik e s tru cture. Alm os t so l ely m ono nu cl ea r
infl a m ma t o ry ce ll infiltra ti o n is sca nty. H ae m a t oxy lin -va n Gi eso n s t a inin g.
X 160.
 37

Fig. 5 .
Th e mini a tyrc glandular lumin a so m etim es occurring in diffuse ca r cin om as. Th e
cell s arc not polarized a nd coJTcspond s tru ctur all y th e o th er· cell s of diffu se car-
cin oma. H acmal oxy lin-mu cic a r·minc s t a ining. X 160.

th ese colloid carcinomas regularly di splayed the original structure of

th e diffuse carcinoma.
Th e hi stoch emical properties of mucu s did not differ di s tinctly in
the intes tinal-type and diffu se carcinomas. The secretion stained as
pure acid mucu s in 44 per cent (58/132) of the intes tinal -type carci-
noma s. Slightly more frequently (in 52 per cent, 69/132) th e sec retion
s tain ed in addition to acid st ains with Bes t' s carmine which demon-
strates n eutral mucus. Cases in which th e mucu s of intes tinal-tyj) e car-
cinoma stained in th e m ann er of purely n eutral mucu s were few ( 4 per
cent, 5/132). In diffuse carcinomas, two kinds of secre ting cells often
occurred in the sam e tumour. It is poss ible that th ey r ep r esented two
different sec retory phases of th e sam e cell type. One cell type contained
more profuse, th e other more scanty mucus. The mu cus of the former
u sually stain ed like acid mu cus or, both r eac tion s might be positive.
The secretion of th e latter almost a lways sta in ed like neutral mu cu s .
Thu s, 88 p er cent (81 /92) of th e diffu se ca rcinomas co ntain ed secre ta
which sta ined in th e m ann er of acid as well as of n eutral mu cu s. Th e
secreta stained purely like neutral mu cu s in 10 per cent (9/92) a nd
purely like acid mucus in 2 per cent (2/92) of the cases .
As r ega rd s enterochrom a ffin cells, both argy rophil and argentaffin
cells were encountered in both carcinoma t ypes . However, tumours
 38

F ig. 6- 7.
Fig. 6. Sec r e ti o n o f mu cu s in intes tin a l - typ e ca r cin o m a. Onl y a few sec r e tin g cell s
a r e br o u ght out h y PAS . Th e mu cu s fo rm s a di s tin c tl y d e fin ed th eca in th e
middl e o f th e cell. Th e gl a ndul a r lumin a co ntain a g r ea t er qu a ntity o f
sec r e t ed mu cu s. P AS t echniqu e. X 160.
Fig. 7. Sec r e ti on o f mu cu s in diffu se ca r cin om a. Th e m a j ority o f th e tum our cell s
co nt a in mu cu s. It is eve nl y di s t r ibut ed in th e cy t opl as m a nd th er e fore see m s
to b e indi s tin c tl y del imit ed . P AS tec hniqu e. X 160.
 39

with enterochromaffin cell s were considerably more frequent and th e

cells w ere more profuse in diffus e than in intes tinal-typ e ca rcinom as.
111ode of growth. Intestinal-type ca rc inom a u su a ll y sp read to a
clea rly and often di stin ctl y defin ed area. The type of tumour ti ssu e
varied in th e different parts of th e ca rcinom a; a tumour forming large
glandular lumina in th e ce ntre co uld be sc irrhou s at th e m a rgin of its
sp read, fr equ ently formin g only small, solid, cell co rd s . Th e original
intestinal-type cell s tructure was di stin ctl y visible even in su ch peri-
pheral areas. Diffu se ca rc inoma did not form as well def in ed tumou rs .
Th e mod e of g rowth of th e tumour ti ssu e at th e m a rgin of th e spread
did not differ from mod es of g rowth in th e other parts of th e tumour .
Generally the intes tinal-type carcinoma did not spread more widely
in th e mucosa tha n above th e infiltratin g part of th e tumour. It tend ed
to ul cerate over th e entire area in whi ch it reached th e mu cosa. Diffu se
ca rcin oma was charac terized by a wider sprea d in sid e th e mu cosa
(co ntiguou s plaque phenomenon, Collins & Gall 1952). Th e infiltrated
mu cosa was oft en preserved from ul cera ti on because of th e sup erfi cia l
parts of normal mucosa that were revealed.
Connective ti ssu e proliferation varied quantita tively in both types ,of
ca rcinoma . How ever, th e almost m ed ull a ry mod e of g rowth en-
countered fairly frequ entl y in th e intes tinal-type ca rcin o ma s was rare
in diffu se carcinom as. Scirrhou s s tructure was more t ypi ca l of diffu se
ca rcin oma s, hut wa s not ra re in ca rc inomas of intes tinal ty pe. Scirrhous
structure originated occas ion all y in diffu se ca rcinoma s also without
sli·o mal prolifera tion, th e tum our cell s sprea din g es pecia ll y in th e
tuni ca mus culari s a nd serosa in fa irl y s parse clusters.
The inflammatory cell infiltration p e rtainin g to ho s t reac ti on a nd
ind epend ent of ul ce ra ti on s o r n ec roses was u sually profuse in intes tinal -
type carcin omas ; it co uld he ve ry pronounced and, if so, was form ed
large ly of polymorphonuc lea r leucocyles . In seve ra l cases th e inflam-
ma tory ce ll infiltration was co ncentra ted a t th e margin of spread of
th e tumour. It was mo stl y more faint , so me tim es very s li ght in diffu se
ca rcino mas; th e inflammatory cell s were u suall y mon o nu clea r.

CO RH E LATION S BE TW EEN I NTES TI NA L - TYP E

AND DIFF USE GAST RI C CARC I NOMA AN D OTHER
C HARA CTER I ST I CS OF THE DISEASE

Sex. Th e g rea t m ajority, 65 pet; cent (465 pa ti en ts) of th e cases with

intes tinal-type carcinoma were m en , 35 · per cent (25 0) "vomen. Th e
prepond eran ce of m en was di stinctl y less marked among pa ti ents with
diffu se carc inoma: Men 54 per ce nt (24 0 ), women 46 per ce nt (20 1).
Age. Th e m ean age of th e patients w ith intes tin al-ty pe ca rcinom a
was 55.4 years (ca lcul a ted hy decade g roups), th e age of patients w ith
diffuse carcinoma bein g clea rl y lower, 47.7 yea rs . The age di stributi on
was distin ctl y different in both group s (Tabl e l a). Thirteen per ce nt
 41
of the patients with intestinal-type carcinoma were below the age of
50; the peak incidence was seen in the age group 60- 69 years, 55.6 per
cent of the patients were above 60. A distinctly greater proportion, 37.1
per cent of the patients with diffuse carcinoma were below the age of
50, the peak incidence being seen in the age group 50- 59 years and
30.5 per cent of the patients were above the age of 60 . The proportion
of diffuse carcinomas in all gastric carcinomas was 70 per cent in th e
age group below 40 years but only 22 per cent in the age group above
60 years (Table 1b).
TABLE l a
Age Distribution of Patients with lnt es linal-TIJp e and Diffuse Gastric Carcinoma.

ITotal 10- 20- 30 - 40 - 50- 60 - 70 -

I 80 -
Intes tinal -type cases 701 17 74 220 282 106 2
carcinoma % 100 2.4 10.6 31.4 40.2 15.1 0.3
Diffu se cases 429 2 5 50 102 139 96 35
carcinoma % 100 0.5 1.2 11.6 23.8 32.4 22.4 8.1

TABLE 1b
Proportion of Diffuse Gastric Carcinomas in all Carcinomas in th e Diffe r~~ nt
Aae Groups .

Be low A hov e
Tot a l 40 yrs. (iO yrs .

All ca t·ci noma s cases 1312 82 196 425 609

Diffu se ca. cases 429 fl7 102 139 131
% 70 52 33 22

Changes in th e normal mucosa close to the tumour (Table 2a). The

gastric mucosa in the immediate vicinity of intestinal-type carcinomas
was more rarely of a normal or near-normal structure than in diffuse
carcinomas ( 10 and 23 per cent). Marked signs of chronic atrophic,
atrophic-hyperplastic, or hypeq)lastic gastritis in the surrounding mu-
cosa were encountered in 88 per cent of th e intestinal-type and in 45

Fig. 8- 9.
Fig. 8. Colloid carcinoma devel o ping ft·om a n int estinal -type carc in o m a. The ep ith e-
lium o f the glandular lumina of !h e ade n ocat-cin oma, also see n in th e
picture, becomes more shallow on account of th e profuse secre tion and
breaks; lo ose pieces of th e columnar ep ithelium arc see n in th e mucus
masses. Haemaloxylin -va n Gieson staining. X 100.
Fia. 9. Collnirl carcinoma devel oping ft·om diffuse carci n oma. In th e middle o f th e
pict ure is a part of th e original diffuse carcinoma, with h eavy secreti on of
mucus. The cell s of th e colloid ca t·cinoma part are situa t ed in th e middle of
the mas ses of mucu s, e ith er isolated or in lo ose clu s ter s, but th ey do not
form pieces of continuous epi thelium. Haematoxylin-van Gi eso n sta ining.
X 100.
 42

per cent of the diffu se ca rcinom as. The mucosa around diffus e car-
cin oma fairl y often (32 per cent) di splayed high fold formation which
was covered by gas tric surface ep ithelium and differ ed from th at oc-
curring in chroni c gastriti s. Simil a r fold formation was en countered
onl y excepti on all y in carcinom as of intes tin al type.

TABLE 2a
Ch anges in th e Mucosa S urr ounding th e Carc in oma in lnl es linal-Tup e
an d Diffuse Gas / ric Ca rc inomas.

Total Nearly Chronic I ricia

Laq,:c s up e r-
l e pith e-
no nn nl gas triti s
li a l fo ld s

In les t in a !-type cases 329 34 288 7

carc in om a % 100 10 88 2
Diffus e cases 271 62 123 86
ca r c in oma % 100 23 45 32

TABLE 2h
Occ urr en ce of Jnt cs linal Met ap lasia in th e Mucosa S u rrou ndin g th e Carcin oma in
Jn/ e.s lin al-Tupe and Diffuse Gas tric Carcin om as.

T o ta l Ahsc nt Scan ty Fairly Pro fus e

p rof u se

Int es tin a l - type cases 5:16 48 132 157 199

carci n oma % 100 9 25 29 37
Diffu se cases 324 14;) 101 54 24
carci nom a % 100 45 31 17 7

Intes tina l metaplasia in th e surrounding mu cosa was dis tinctl y more

frequent and widespread in intestin al-type than in diffu se carcinom as
(T ab le 2b). Metaplasia in th e normal mu cosa includ ed in th e s pecim en
was absent in 9 per cent of the intes tin al- type and in 45 per cent of
the diffuse carcin omas . On the other h and, profuse or fairly profuse
m etapl as ia was present in 66 per ce nt of th e intes tin a l-type and in 24
per cent of the diffuse carcinomas. The difference in the inc idence of
intes tina l m etap las ias in intes tina'l-type and diffuse carcinomas em-
erged in a ll age g roups. In th e age g roup below 50 years, cases without
metaplasia in th e mu cosa tota ll ed 15 per cent (9/62) in intestin al-type
carcinom a, 58 per cent ( 771132) in diffuse carcinomas; in patients
aged 50- 59 th e percentages were 12 (191156) a nd 39 ( 44/112 ), respec-
tively; in patients above 60-years it was 7 (18/253) and 20 (20/99)
per cen t.
The macroscopic f ea tures of th e tumour showed so m e co rrela tion
w ith th e hi stolog ical main t ypes. Of the intes tin a l-type ca rcinom as,
60 per cen t (2 15/361) were described as polypous o r fungating; th e
corresponding perce ntage in diffu se carc inom as was 31 ( 73/235). An
equally great proportion both of intes tin a l-type (25 per cent ) and
 43

diffu se carcinom as ( 26 per cent) w er e r eported to be excavatin g

tumour s. Intes tin a l-type ca rcinoma fo rm ed m o re r a rely an infiltrate
of th e liniti s pl as ti ca ty pe ( 15 per ce nt ) th a n diffu se ca rcin oma s ( 43
p er cent ) .
Th e l ocalizatio n of th e tum our in th e s tom ach di spl ayed n o definite
co rrelation with th e hi s tolog ical type. Fifty fiv e p er cent ( 277/498 ) of
th e intestinal-typ e carcin om as and 60 per ce nt (183/306 ) of th e diffu se
ca rc inom as we re seen in th e pylo ru s and antrum, 31 (1 52 ) and 29
pee cent (88 ) , r espec tively , were a t sites hi gh er up in th e lesse r curva-
tmc and in th e hody, a nd 13 (62 ) a nd 4 pe e ce nt ( 13) in th e ca rdi a .
One p er ce nt ( 7) of th e intes tinal-ty pe and 7 per cent (22 ) of th e diffu se
ca rcinoma s h a d s prea d throu gh out th e s tom ac h wall.
Prognos is. To a ssess th e prognosis , a m a teri al of 153 p a ti ents wa s
avail able to w h om cura tive trea tm ent w as given (l.aurcn cl al. 1962).
In thi s se ri es intes tinal -type ca rc inom a h ad m os t favour abl e prog nos is.
The pos top erative survi val rate w as below 1 year in 22 p er cent of th e
cases of intes tin a l-type and 32 p er cent in cases of diffu se ca rci nom a,
whil e 36 and 32 p er cent of th e p a ti ents, r es pec ti vely, li ved fo r 1- 3
yea r s, a nd 43 and 35 per ce nt fo r more than 3 yea rs .

DI SCUSSION

\Vhil c adenoca rcinom as o f intes tinal -ty pe h ave been ra th e r ea sy to

cla ssify hi s tologicall y, diffu se ca rcin om as cau se m o re probl e ms a nd
opinion s differ as to th e n a ture of these tum ours. Th e te rmin o logy
a pplied to diffu se ca rcin om as is divc i·sifi cd and th e types of tum ou r
includ ed in th e vari ou s, a rbitraril y fo rm ed g roup s a rc d iffcrcnl .
Krompech er (1010 ) r egard ed so m e of th ese tum ours as infl ammatory
ch an ges and empl oyed th e old n a m e liniti s pla s ti ca whi ch is su gges ti ve
of inflammation . The t erm m ost comm onl y u sed h as bee n scirrh ou s
ca rcin om a (e.g . V er se 1008 and B orrmann 1026 ) . Usu all y thi s g roup ,
h oweve r , h as in clud ed a denoca rc ino m as containin g p rofu se s trom a.
B orrmann al so describ ed diffu se ca rc in om a a s a se pa ra te ty pe, whi ch
is in closer ag reem ent with th e present auth or 's spec ifi ca ti on of th e
diffu se ca rcinom a typ e. Other desc ri ptive class ifi cati on s corres pondin g
m o re or less h erewith arc : solid diffu se ca rcin oma ( Tu o mikoski 1!)37 ),
fihrou s carcin om a (l{onj elzny 1038), mu ciparou s scirrhu s ( Ekr•r &
E{skind 1952 ) , di sseminated ca rcinom a ( u. f llb erlini 1955), diffu se
sc inhou s carcin oma ( Euan s 1056 ) nnd undifferenti a ted ca rcin om a
( Takagi & Som cya 1959 ) . A numb er of rc j1orts in th e liter a ture su ggest
th a t diffu se ca rcin om a is a n independent ty pe of tum our· whi ch differ s
fr om other gas tri c ca rcin om as . Saphir & Park er (1 943) r ega rd linitis
I1las ti ca a s a sepa rate entity in whi ch small cell s m ay h e tra nsfo rm ed
into s ign et rin g cell s or , occasion a ll y, form mini a tu re gland s. Hamp er[
0052) r efer s to scirrhu s as a separa te t y pe of tum our and draws th e
a ttenti on to th e unu su a l m ode of mu cu s secre ti on an d th e p resen ce of
 44

enterochromaffin cells. Mucous cell carcinoma was by Mulligan & Rem-

her (1954) considered to be a histogenetically specific tumour with its
own biologic behaviour. Nagayo & f{omagoe (1961) stated in their
study on mucosal carcinomas that diffuse carcinomas which meta-
stasize as single cells constitute a basic type of their own which does
not change into an adenocarcinoma forming definite glands.
The specific difference between intestinal-type and diffuse carcino-
ma revealed by structural study is corroborated by comparative ob-
servations of the structure of the primary tumour and the metastases.
The present material included 202 cases with lymph node metastasis.
As a rule the structure of the tumour tissue in the lymph node would
correspond to the main type of primary tumour. Usually structure of
intestinal-type carcinoma would be differentiated equally far in the
metastasis and in the primary tumour. The cells of diffuse carcinomas
were often larger in lymph node metastases than in the primary
tumour. During proliferation in the sinuses the cells would often form
dense masses and thus the tumour tissue might be more solid than
tissue in the primary tumour. Several other investigators have also
reported that the basic type of gastric carcinoma remains the same
when the tumour spreads, but that variations occur because of topical
conditions at the growth site (Bohmig 1937, Oola & Tanaka 1951b,
1952, Tauchi & Sa to 1958, Tauchi et al. 1960).
The histological structure of a gastric carcinoma can remain un-
changed for a longer period which feature is evident from the 13 cases
in the series in which the tumour recurred more than one year after
the first operation. The structure also of the new tumour, was usually
of the same sub-type as that of the primary tumour. As emphasized
by Willis ( 1960), the occurrence of true progression by which the
structure of a tumour is changed is a rare phenomenon.
Oola & Tanaka ( 1951a) turned their attention to the difference
of the type of inflammatory cell infiltration in intestinal-type and
in diffuse carcinoma which feature has been established in the present
study. They attributed the marked inflammatory ·cell infiltration seen
in adenocarcinomas to infection of the secretion retained in the
glandular lumina. An argument against this theory is the finding that
colloid carcinomas of diffuse type usually display only scanty inflam-
matory cell infiltration. In the opinion of the present author, a more
probable explanation of inflammatory cell infiltration unrelated to
ulceration and necroses is the reaction of the organism to carcinoma.
This hypothesis was advanced e.g. by Black el al. (1954) and Larmi &
Saxen (1963). This part of the host reaction seems to be of a different
nature in intestinal-type and in diffuse carcinoma. The other component
of the host reaction, .the proliferation of connective tissue, is also
different in the two types of gastric carcinoma.
Comparison of the structure of the tumour with tl1at of carcinomas
of the colon was one of the criteria used for the definition of the
 45

intestinal-type carcinoma. For this compa ri son, the material obta in ed

in a n earli er inv es ti gati on w as u sed ( Lauren 1961) . Althou gh all th e
sub-types of intes tin al-typ e gas tri c carcinom a occur in ca rcinomas o f
th e co lon as w ell, th e in cid ence of th e va riou s sub-typ es in th e in-
tes tin es differs from th e in cid en ce in th e s tomach. Th e m os t signifi ca nt
differen ce is the more profu se occurren ce of p a pill a ry s tru ctures in
ca rc inomas of th e col on . It is poss ibl e that th e difference is du e to th e
different mod e of ori g in. Ca rcinom as o f th e colon obviou s ly a ri se
m os tl y from ad cn op a pillo ma s, gas tri c ca1·cinomas, in contras t, from a
chan ged but not polypou s mu cosa . The diffu se type is fairl y rnrc
am ong ca rcinom as of th e col on. Th e present auth or h as en countered
onl y two diffu se carc inoma s assum ed to be prim a ry in th e intes tin es.
One of th ese wa s found in a gi rl aged 13, in th e fl exura li cn a li s of th e
co lon ; th e other d erived from th e rectum. It was n ot poss ibl e in an y
of th ese ca ses to rul e out th e poss ibility o f a co nco mitant ga stri c car-
c inom a. The rarity of diffu se co loni c ca rcin om a h as also b ee n reported
in th e literature ( Laufman & Saphir Hl 51, Fahl el al . 1960 ) , toge th er
·w ith the fac t th a t when these ca r cinom as ac tu a ll y occur in th e in-
t es tin es th ey a re m etas tases of gas tri c ca rcin o m a ( Dixo n & St ev en s
1936 ) .
As diffu se ca rc in om as h ave n o gla ndul a r s tru cture th ey a rc always
class ifi ed in the m ost m ali gnant g rad e in the hi s tolog ical Bro d crs- ty pe
m a li gn an cy g ra din g (Brod ers 1942 ) , bein g r ega rd ed as undiffere nti a ted
tum ou rs . Howeve r, seve ra l features in th e s tru cture o f diffu se ca rci-
n om as d en ote th a t th e diffe rentiati on of their cell s ha s prog ressed fa r.
Sec reti on of mu cu s is m ore co mm on as well as m o re p ro fu se in th ese
tum ours th a n in int es tin a l-ty pe ca rcin om as. Enteroc hromaffin ce ll s
arc en co untered m ore o ft en . The ch a racteri s ti cs of m a li gn a nt tum ours,
ce llul a r atypi a, a nd num erou s mito tic fi gures arc m o re pro min ent in
intes tin a l-ty pe th an in diffu se ca rcinom as. Th e eva lu a ti on o f mali gn-
an cy on the bas is of th e mi c roscopi c s tru cture h as n o t been as sa ti s-
facto ry in cases of gas tri c ca rcinom as a s in the g radin g o f o th er carci-
n om as (S chindler el al. 1041, St ein er cL al. 1048, H oe rr 1954, L ewin
1960 ). Howeve r, it is kn own th a t the prog nos is is poorer in diffu se
than in intes tin a l-ty pe ca rcin oma s, w hi ch is a lso horn out in th e
p resent m a terial. The reason h ereo f m ay be so m e fea ture o th er th a n
a m o re ra pid prolifera ti on o f th e tum ours ca u sed hy m ali gn an cy. Dif fu se
carc in om as spread eas il y as individu al ce ll s o r in s m a ll cell clu s ters in
th e ti ssu e spaces ove r an ex tens ive a rea. They do n ot fo rm th e di s tin ct
m a rg in o f s pread whi ch is o ft en typi ca l o f intes tin a l-typ e ca rcin o m as
a nd th e ex is ten ce of whi ch is important fo r a favo urabl e prog nos is
(Murakami el al. 1959, Eker & Efs kind 1960 ). Ano th er factor in th e poo r
prognos is is th at di ag nos ti c sym p tom s in th ese tum ours m ay be r et arde d,
viz . s tenos is and ul ce ra ti on s, a nd th erefo re tum ours m ay h ave develo ped
to th e in operable s tage b y th e tim e th e pa ti ent is a dmitted for trea t-
m ent. It is obviou s th a t sepa ra te cr iteria mu s t be es ta bli sh ed for lh e
 ' ~
• _t.:•

46 ..,

appraisal of the histological malignancy in intestinal-type and in diffuse

carcinomas.
The high incidence of diffuse type tumours characteristic of gastric
carcinomas in the young age groups has also been established by se-
veral other investigators ( Oota & Misu 1!HiH, Lewin 1960, Tamura &
Curtiss 1960, Nagayo & J{omagoe 1!)61). Jiirvi & J.rmrhz (1 !)51), Sa to
et al. ( 1959) and Tau chi l'l al. (1 !)60) found, correspondingly, that
carcinomas in older patients mostly are adenocarcinomas. The rela-
tively high incidence of diffuse carcinoma in women has also been
noted by Lewin ( 1960) and Tamura & Curtiss ( 1!)()()).
Opinions on the pathogenesis of gastric carcinoma have been highly
conflicting on the point whether or not carcinoma is preceded by
chronic gastritis with intestinal metaplasia. Especially the workers
(e.g. Tuomikoski 1936, Siurala & Seppiilii 1960) who were familiar
with Saltzman's (191:~) and Konjl'lzny's ( Hl28, 1!l38) studies, regard
chronic gastritis as pathogenetically important. But its importance is
denied by several Anglo-Saxon authors (e.g. Guiss & Stewart 1!)43,
Magnus 1946, Hebbel 19-Hl). Sclzindler (1940) and Morson (1 !l56)
postulate that a part of carcinomas arc preceded by gastritis. The
present authors's observations suggest that the precancerous change in
tht> mucosa is diffpn•nt in intl•stinal-typt- and in diffuSl' carcinomas.
Chronic gastritis and intestinal metaplasias in the mucosa around the
tumour tissue arc often lacking in diffuse carcinomas, as Nauauo &
Komagoe (1961) also have set-n in their study on supl'rficial carci-
nomas. In intestinal-type carcinoma, on the other hand, the tumour
almost always borders on the mucosa which shows chronic gastritis
and metaplasia. On the other hand, similar high fold formation covt-recl
by surface epithelium of the gastric mucosa to that seen on the mar-
gins of peptic ulcers arc often seen on the houndarit-s of diffuse carci-
noma. Oota & Misu ( Hl59) reportt-d that 5!l.:J per cent of the diffuse
carcinomas in their series originated in pPptic ulcer. It was not
possible in the present series to examine sufficiently thoroughly the
correlation between ulcer and carcinoma. However, the precancerous,
morphologically demonstrable lesion seems to be fairly limited re-
gionally in diffuse carcinoma, whereas intestinal-type carcinoma is
preceded hy chronic gastritis in an extensive area of the mucosa. The
predominance of women among patients with diffuse carcinoma and
the young age of these are probably also indicative of the different
character of the lesion preceding this carcinoma type as compared with
the lesion preceding intestinal-type carcinoma (Jiirvi & J.auren Hl51,
p. 39, Tahle 8).
The present study shows that intestinal-type and diffuse gastric
carcinoma, which include the large majority of the gastric carcinomas,
constitute two histological basic types which are individually different.
There is no requirement for a more detailed descriptive classification
in examination and in routine diagnostic. The classification into diffuse

:.- ....
 • 47
and intes tin al-type ca rcinoma s is easier and m ore reliable than th e
sys tem s u sed in earli er m ethod s . Thi s class ification may serve to
improve the compa tibility of different gastric ca rci noma s tudi es.
Th e principal signifi ca n ce of differ enti a ti on between intes tin a l-type
and diffu se gas tri c ca rcin oma is, however, that th e tum ours of these
two types differ n ot only s tru c tura ll y but also in th ei r other char-
ac ter isti cs . Such difference is not a llowed fo r in the purely desc rip tive
histol og ica l types of gas tri c ca rcino ma in co mm on u sc. Th e observations
mad e h ere motivate th e ass umption that intes tinal-type and diffus e
ca rcin om a mi ght h ave an a t leas t som ewh a t differin g ae ti ology and
pa th oge nes is.

SU M l\1 AnY
Two hi stologi cal main types cou ld be distinguished in gas tri c ca rci -
nom as hy a stru c tura l and hi s toch emical stud y of a surgica l material
compri sin g 1,344 cases. "Intestinal-type ca rcinom a" accounted fo r 53
per cen t and "diffu se ca rcin om a" for 33 per cen t of all th e gas tri c
carcinom as . The ca rc inomas of th ese m a in t ypes had th eir own typi ca l
features of gen eral structure and cell stru cture, secr eti on of mu cu s and
mode of grow th. Th e propo rti on of m en and older patients was g rea ter
in th e intes tinal-type g roup th a n in th e g roup of diffu se ca rcin o ma.
Gash·itic ch an ges in th e surroundin g mu cosa and th e incid en ce and
ex tent of intes tinal m etap las ias were grea te r in intestinal-type ca rci-
nomas. The progJ1osis was poorer in diffuse th an in intes tin al-type
carc inom as .
As intestinal-type a nd diffu se gastri c ca rcin om a differed n o t onl y
s tru ctura ll y but also in th eir co rrel a ti on to th e o th er ch arac teri s ti cs
of th e di sease, it mi ght be assumed th a t th ey, a t leas t to so me ex tent
arc cau sed by different ac tiol og ic factors and th a t th ey differ paUlo-
gen eti call y as well.

nEFEnENCES
Ack erman,!, V. & del R eaato , J . A.: Cancer. Diagno s is, tr ea tm en t , a nd prognos is. Th e
C. V. Mo sby Compa ny, Sa int Lo ui s 1962 .
v. Alber tini, A.: Hi s t ol og isch e Gesc h w ul s tdi agnos lilc Sys t ema li sch e Mo rphol og ic dcr
m c n sc hli ch c n Gesc h w Ul s tc a l s Gl'llndl age flir di e klini sc h c Bc n r tc ilun g. Geoq{
Thi eme Ve rl ag, Stutt gm·t 1 95~ .
lllaclc, M. M., Opfer , S. R. & Sprer, F . D.: Mi c•·oscop ic structur e o f ga s tri c cn r c in o ma s
and lhcil· reg ion a l lymph nod es in re l a ti on t o su•·viva l. Su rg. Gyncc. Ohs t et.
98: 725- 734,1954.
Bolrmia, R.: Di e m orp h ol ogisch fa ssh a ren ' Vac h s tum sl'(csc t zc drii scn hild c nd c r J{ar-
zinom e un d ihr e r· l\ !ctas t asc n . Vcrh . dtsch. p a th . Gcs. 30 : 329- 337, 1937 .
B orrmrmn , 1?.: Ge schwulstc des 1\Iagc n s un d Du o d enum s. In : H a ndbu ch d c1· s pczicll en
J)a th ol og isch cn An a t omi c unu Hi s t olol'( ie v . H cnlic-Luha r sch . Bd. IV, 1. .Ju liu s
S prin ge•·, Berlin 1926.
/Jrod ers , A. C.: Carcin om a and o th er malignant lesio n s of th e s t omach : Pa th ol og ic
co n s id er a ti on s. In: ' Va lt c J·s-Gray-Pr ics tl ey: Ca •·cin oma and o th er m ali g n a n t
lesio n s of th e s t o mach . " '· U. Sa und ers Com pa n y , Phil a d. a nd Lo nd o n 1942.
Co llin s, W.T. & Gall, E. A. : Gas tri c ca rcinom a : a multi ce ntri c l esion. Cancer ( P hil a d.)
5: 62- 72, 1952.
 48
Dixon, C. F. & Stevens, G. A.: Carcinoma of linitis plastica type involving the in-
testine. Ann. Sur!-(. 10:1: 2G:l-272, 1936.
Eker, R. & Efskind, J.: Investigations on the intramural spread of gastric carcinoma.
Acta path. ct microhiol. scandinav. 30: 371-383, 1952.
Eker, R. & Efsldncl, J.: The pathology and prognosis of gastric carcinoma. Based on
1:114 partially and totally resected cases. Acta chir. scandinav. Sup pl. 264:
1-182,1960.
Evans, It W.: Histological appearances of tumours. E. & S. Livin!-(stonc Ltd., Edin-
hurl(h and London, 1956.
Fahl, J. C., Duckertu, M.JJ. & Judd, E. S.: Scil'l'hous cm·cinoma of the colon and
rectum. Surg. Gyncg. Ohstet. 111: 759-71Hi, 1!Hi0.
Guiss, L. W. & Stewart, F. lV.: Chronic atrophic gastritis and cancer of the stomach.
Arch. Surg. (Chicago) 4fi: 823-843, 194:i.
IIamperl, II.: Oher arl(yrophilc Zcllen. Virchows Arch. path. Anal. 321: 482-507, 1952.
IIamperl, II.: Die 1\lorpholol(ie der Tumoren. In: BUchner: Handhuch de1· all!-(cmcincn
Pathologic. Bd. VI, :1. Sprinl(er, Bcrlin-(;iittin!-(cn-Hcidelhcrl( 1!151i.
llebbel, R.: The topography of chronic gastritis in cancer-hearinl( stomachs. ,J. nat.
Cancer lnst. 10: 505-522, 1949.
llenschen, F.: Die Pathogenesc des Magenkrehses. Arch. "de Vecchi" .'Jt: 149-1li2, l!HiO.
Hoerr, E. 0.: A sur!-(eon's classification of ca1·einoma of the stomach. Sur!-(. Gyne!-(.
Ohstet. 99: 281-286, 1954.
Jarvi, 0. & Laurh1, 1'.: On the !'Ole of heterotopias of the intestinal epithelium in the
patho!-(encsis of l(astric cancer. Acta path. et microhiol. scandinav. 29: 2H-44,
1951.
Jarvi, 0. & Laurt:n, 1'.: Gastric glandular tumours provided with excretory ducts, and
criticism of the thc<H'Y of the tumours arising in heterotopic pancreas. Ob-
servations on the occurrence of atypieal glands in the stomach. Acta path. et
microhiol. scandinav. (i2: 1-2:1, 19li4.
Kunjetzny, G. E.: Die Entziindungcn des l\lagens. In: Handhuch dc1· spcziellcn patllo-
loJ.lischcn Anatomic und Histologic v. Hcnl<e-Luharsch. Bd. IV, 2 ..Julius Sprin-
ger, Berlin 1!)28.
Konjl'lzn11, G. E.: Ocr l\lagenl<rehs. Ferdinand Enlw VerlaJ.l, Stuttgart 1938.
Krompecher, E.: Zur Anatomie, llistolol(ic unci Pathogcncse der l(astrischen und
gastrointestinalcn Skh·I·ostenose. lleiii'. path. Anal. alii(. Path.-~-!); :i84-42!1, 1!110.
Larrni, K. I. & Sa.ren, L.: "Host reaction" in gastric cancer. A preliminary study of
119 cases of gastn•ctomy. Acta chir. scandinav. 125: 144--14H, 1963.
Laufman, II. & Saphir, 0.: Primary linitis !llastica type of carcinoma of the colon.
Arch. Surg. (Chicago) fi2: 79-!Jl, 1951.
Lauren, P.: The cell structure aJHI scc1·ction in intestinal cann•r with reference to
benign epithelial tumours of the bowel. Acta path. ct microhiol. scandinav.
Suppl. J.'i2: 7-151, 1!Hil.
Lauren, P.: Diffuse and intestinal types of gastric carcinoma-two pathol(cnctically
independent diseases. Proceed. XIV Scandinav. Path. and 1\Iicrohiol. Cong1·.
Oslo 19H4, p. 119-120. Universitetsforlaget, Oslo 19H4.
Lauren. J>., Viilwri, S., Ilyttinen, A. & Autio, V.: Pathological features of gastric
cancer affecting survival after curative resections. Ann. chir. et gynaec. Fenniae
51: :142-:150, 19H2.
Lewin, E.: Gastric cancer. A clinical study with I'cfei·cm·e to total gastrectomy and
microscopic grading. Acta chir. scandinav. Sup pl. 2fi2: H-ll!J, 1!Hi0.
lllagnus, II. A.. : The pathology of simple gastritis. J. Path. Bact. 58: 431-439, 1946.
Morson, B. C.: Carcinoma arising from areas of intestinal metaplasia in the gastric
mucosa. Brit. J. Cancer 9: 377-385, 1955.
Morson, B. C.: Intestinal metaplasia of the gastric mucosa. Gastroenterologia 86:
353-355, 195H.
Morson. B. C.: PI·ccancerous lesions of upper l(astrointestinal tract. J. Amc1·. 1\Ied.
Ass. 179:311-315, 19H2.
Mulligan, Il.lll. & Rember, R. R.: Histogenesis and biologic behavior of gastric car-
cinoma. A.M.A. Arch. Path. 58: 1-25, 1954.
Murakami, T., Chin, Y., Watanabe, Il., Hirafuku, 1., Tashiro, K., Sagawa, F., Tanaka,
T., Suaimura, T. & Kubota, K.: Studies on the metastasis of gastric cancer
(Report 2). Gann Suppl. 50:203-204,1959.
 49
N agay o, T. & Komago e, T.: Hi st ol og ical s tudi es of ga stri c mu cosal can ce r with
special r efe r en ce t o r el a ti o n ship of hi s t ol ogi cal pi ctures b e tween th e mu cosal
ca n cer a nd th e can ce r -b earin g gas tri c mu cosa. Ga nn 52 : 10H- 119, 1961.
Oot a, K. <~ Misu, Y. : On th e hi st oge n es is. o f scir rh ou s carcinom a of th e s t om ach.
Ga nn Sup pl. 50: 15{}-151, 1959.
Oota, K. & T an aka , !If. : On th e signifi ca nce of ca n a li cular infec ti o n in gas tr ic ca n ce r.
Ga nn lf 2 : 168- 172, 1951 ( a) .
Oota, K. & Tanak a, M . : On pl co m o rph y in ca1·cin om a. Ga nn 42 : 181- 187, 195 1 (b ).
Oota, K, & T an aka, M. : Colliding caJ·cin om as o f th e s to m ach . (A co n s id c1·a ti o n o f
hi s t ogen es is o f a s ingl e m ali gn a nt tum o1· in ge n er a l. ) Ga nn 4' 210- 212, 19 52 .
R a iford, T. S. : Mu co id ca r cin om a of th e gas tr o-intes tin al trac t; so called co ll oid c--···
ca ncer . Su1·g. Gy n ec. Ob s te t. 55 :409- 417, 1932 .
Salt z man , F .: Studi e n iib er Mage nkreb s mit h eso nd c1·er Berii ck si chti gun g dt r Ver-
iind erung cn i n dcr Mage n schl eimh a ut und dc r im Tum o r und a n d csse1. Ha nd
a uft1·et e nd en Rund ze ll cninfilt ra ti o n . Arh . Pa th . In st. Uni v. Helsin gfoi·s N.F.
1: 335- 440, 1913.
Saphir, 0. & Park er, M. L .: Liniti s pl as ti ca ty p e of ca r cin om a . Surg. Gynec. Oh s t ct.
76: 206- 21 3, 1943.
S ato, 1'., T ak euchi, J. , K obayashi, li. , Kawabe, W. & T auchi, 11.: Helati on ship b e tw ee n
age of th e case a nd hi s t ol og ical p ictur e of gas tri c ca n cer a nd its lli stol og ical
ch a n ge in th e p rocess of gr owth . Ga nn Sup pl. 50: 151- 152, 1959.
Schindler, R.: Ea rl y d iagn os is a nd prog n os is of gas tri c carcin om a. J. a m e1·. Med . Ass.
115 : 1693- 1699,19 40.
Sch indl er , R . : E a rly di ag nos is o f ca nce r o f th e s tom ach: gas trosco py, a nd gas tri c
bi op sies, gas tr oph ot ogra ph y, a nd X-r ays . J. n a t. Ca ncer Ins t. 1 : 45 1- 480, 19 41.
Schindler, R .. Stein er, P. E ., S mith , W. M. & Daileu, M. E .: Th e cl ass ifica ti on of
ga s tr ic car cin om a . Surg. Gyn cc. Ob st e t. 73 : 30- 39, 19 41.
S iurala, M. & S eppiilii, K . : Atrophic gas trit is as a poss ibl e precur so r of gas tri c ca r -
cin om a a nd p erni cious a n emi a . R es ult s o f foll ow -up ex a min a ti o n s. Ac t a m cd.
sca ndin av. 166: 455- 474, 1960.
S t ein er, P . E. , Maim on , S. N., Palm er, W . L . & Kirsn er, J. B. : Gas tr i c ca n cc1· : m o rph o-
l og ic fac to1·s in fiv c-yca 1· s urviva l a ft e r gas trec t om y. Am c1·. J. Pa th . 24: 947- 969,
19 48.
S t out , A. P. : Tumors o f th e s t omach. In : Atl as of tum or p a th ol ogy. Vol. XX. Arm ed
F orces In st. P a th. , \ Vas hin gt o n , D .C. 1959.
Tir e S ump os ium on tir e Geographical P a th ology of Gas tr o- int es tin al Cancer: Ac ta
Un. Int. Ca ner. 17 : 283- 286, 1961.
Tak ag i, K. & Som eua, M.: Hi s t o pa th ol ogica l stud y o f mu cosal ca r cin om a o f ·1h c
s t om ach . Ga nn Suppl. 50: 147- 148, 1959.
T amura, P. Y. & Cu r /iss, C.: Cm·cin om a o f th e st om ach in th e yo un g ad ult. Ca ncer
(Phila d. ) 13: 379- 385, 1960.
T au chi, H. & Sal o, T.: Pa th ol ogi ca l inves ti ga ti o n on th e hi s t ol og ica l va ri a ti on of
can cer ti ssu es. Nagoya Mcd. J . -i: 155- 188, 1958 .
T auclJi, H., Sa to, T., K obauaslti, II. & Kaw abe, W.: On th e age fac t o1· i n th e hi s tol ogi-
ca l a p pea r a nce and its va ri a ti o n in gas tr·ic ca nce r. Ga nn 51: 273- 284, 19 60.
Tu omikoslci, V.: Gas triti s und J{ arzin om . Zbl. Chir. 63 : 2022, 1936.
Tu omi/ws lc i, V . : l\1 a h asytiviisUi j a sen l cikk a u s h o id os t a (tl b e1· da s Magc nk a r zin om
unci sein e op er a ti ve Beh a udlun g) . Du odccim ( Hels inki ) 53 : 31- 85, 193 7.
Ve rse, M.: tlb cr di e Hi s togc n cse dcr Schl eimh a utcarcinom c. Verh. dt sch . pa th. Gcs.
12 : 95- 99 , 1908.
W a tt enb erg, L. ~V. : Hi s t och emi cal s tudy of a min op eptidase in m et a plas ia a nd ca r -
cin oma of th e st omach . A.M. A. Arch. P a th . 67 : 28 1- 286, 1959.
W illis, R. A.: Path ol ogy o f tum o ur s. Buttcr wo t·th s, Lo nd o n 1960.

4 ACTA PAT H . 64, 1