Document a4mBwVOkgQzGwXEvNNv7zz8oa
The Pleural Form of Primary Cancer of the Lung
G. BABOLINI and A. BLASI Dis Chest 1956;29;314-323 DOI 10.1378/chest.29.3.314 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://www.chestjournal.org/content/29/3/314
CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright 1956 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://www.chestjournal.org/site/misc/reprints.xhtml) ISSN:0096-0217
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The Pleural Form of Primary
Cancer of the Lung*
G. BABOLINI,
M.D., F.C.C.P. and A. BLASI, Naples, Italy
M.D., F.C.C.P.**
Primary
cancer of the lung in its usual anatomical
manifestations
as-
sumes different
formal aspects on which clinical characteristics
of its
progress and development
largely depend.
In this regard those definitions
which exclusively
refer to anatomic
and
macroscopic
features that characterize
the complete clinical picture of the
disease have bearing, quite apart from the cellular structure
of the newly
formed tissues. It is our intention
to examine hereafter
a particular
anatomical
type
of primary
cancer of the lung, which some researchers
have not taken
into consideration,
but which in our opinion possesses
in reality sufficient
characteristics
of its own to assume special position within the general
picture of this disease. We mean by this the so-called pleural form of pri-
mary cancer of the lung.
This special name is explicitly
mentioned
in the classifications
of P.
Verga,' of Roussy and Huguenin,2
of Olmer and Coll.,3 of Liberti and
Stella,4 of Eizaguirre
: and it is applied
mary cancer of the lung, which rather
to those particular
forms
than affecting
the deeper
of priparen-
chyma, prevalently
acquire a surface development,
spreading
extensively
over the pleura.
It is well known that during the development
of primary
cancer of the
lung, affection of the serosa is a frequent event which is capable of assum-
ing different
features,
such as formation
of pleural effusion;
diffuse or
limited symphisis
or thickening
without any true tumorous
propagation;
localized appearances
of bysmas and neoplastic
masses; metastatizations
in the form of waxen drops or plaques.
These are different
aspects which are in each case to be explained
by
different
stages of development
which mark the general course of the
disease.
The term pleural form of primary
cancer of the lung is, however,
in-
tended to give prominence
to those forms where the manifestation
of
heteroplastic
tissues on the pleura is preponderant
and almost exclusive,
and where the affection of pulmonary
parenchyma
is absolutely
marginal.
The precise definition
of these forms must necessarily
rest, therefore,
not on the external
aspects of the process alone but also on data of an
histological
nature.
In the observations
which have been made by various researchers,
even
those where a fair number of cases are involved, it can be noted that the
clinical picture does not occur with particular
frequency
and that as com-
pared with the most common forms of hilar infiltrations,
either the mas-
*Presented
at the Third International
Congress
on Diseases
Spain, October 4-8, 1954. **From the Phthisiological Clinic of University
and from
Piemonte,"
Naples, Italy (Director:
Prof. V. Mon aldi).
of the Chest, Barcelona,
the Institute
..
"Principi
di
314
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Vol. XXIX
PRIMARY
CANCER OF THE LUNG
315
sive or large nodular type, the cases where pleural affection is involved,
always represent
an extremely
small group. In fact in the case histories
of Verga and Botteri (op. cit.) they appear in three of 30 cases, in five
out of a 100 in those of Liberti and Stella (op. cit.), in four out of 170
in the studies of Sival.6
In our studies, out of 82 cases of primary cancer of the lung, on which
we have complete clinical and histological
documentation,
five presented
neoplastic
affections
of a pleural nature.
In reality in only four of them
have the clinical and radiological
data been supported
by post-mortem
examination
and histological
tests. In Case I in the table the patient died
at home, two days after having left our institute
by his own wish, our
diagnostic
conclusions
are the result of a pleuroscopic
examination
that
permitted
direct visual examination
of the pleura, which was uniformly
invaded by large neoplastic
lumps. Further
deductions
`vere made as a
result of biopsy which made it possible to recognize
bysmas and festoons
of atypical epithelial
elements,
of a cylindric
and cubic type, with a tend-
ency to range themselves
in several rows (Figures
1 and 2).
The individual
course of each of the cases which form part of our col-
lection prompts us to give particular
consideration
to three points which
respectively
concern the clinical and anatomical
course of the disease and
its histological
characteristics.
Table I summarizes
some of the clinical data of greatest importance:
Cases
I :M II : W III : M IV : W
V :M
Age in Years
62
56
68
55
Duration Clinical Course Months
11
6
9
10
43 8
TABLE I
Temp. Fever
subfebrile initially
subfebrile with
occasional
recurrences
subfebrile
with occasional recurrences
Thoracic Pain
++ ++ ++
+--
++
Pleural Eftusion and its Nature
Abundanthemorrhagic Abundant-simple exudative Abundanthemorrhagic
Sacculated-simple
exudative
The subjective
symptomatology
is largely dominated
by the affection
of the pleura, both when this is in the form of a pachypleuritis
syndrome,
without the formation
of effusion (Case IV in our case histories)
and when
there is an exudative
reaction,
of a sero-fibrinous
and sero-hemorrhagic
type, the quantity of which is always considerable
and re-forms
readily.
The latter type is the more frequent.
In the subjective
and functional
symptomatology
which is usually con-
nected with neoplastic
pneumopathy,
from the beginning
thoracic
pain
and dyspnea. are the phenomena
of most importance:
Usually there is no
cough, when present it is slight and transitory,
there is no abundant
ex-
pectoration
or hemoptysis.
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816
BABOLINI
AND BLASI
March. 1956
FIGURE effusion: lung.
1 (CAsE I): Chest x-ray film (July 7th, 1953), after emptying
the pleural
considerable
thickening
of the pleural surface at the left side over collapsed
FIGURE elements
2 (CAsE I): Biopsy
of the cylindric
type.
fragment:
neoplastic
tissue constituted
by epithelial
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Vol. XXIX
PRIMARY
CANCER
OF THE LUNG
317
Modification
of the temperature
curve, in the cases studied by us, seems
to have no particular
trend. In the cases in question there were alterations
of a febrile nature only in the initial phases (Case I), in some cases fever
occurred from time to time, during the whole clinical course of the disease
(Cases IV and V), while in other patients
(Cases II and III) there were
no febrile reactions during the whole course of the disease.
Thoracic
pain, incessant,
unremitting
and refractory
to analgesic
ac-
tion of any kind, are from the beginning
localized in the costal area, and
radiate in a strip along the thoracic wall and towards the shoulders.
Dyspnea,
which is initially connected
with physical efforts and par-
ticular bodily functions,
is considerable
from the beginning
of the dis-
ease. Dell'Acqua7
notes that it appears to have no true connection
with
extent of the exudative
reaction and is caused, more than by any other
factor, by the limitation
of movements
of the thoracic wall, rendered rigid
by the spread of neoplastic
tissue on the surface of the pleura.
The entire course of the disease, from appearance
of the first clinical
data, has in the cases studied by us been from six to 11 months, with an
average duration
of little more than eight months.
This corresponds
ap-
proximately
to figures given by many researchers
with regard to primary
cancer of the lung: Verga and Botteri (op. cit.) : six months; Grissel and
Knox8: seven and one-half
months;
King9: nine and one-third
months;
Liberti and Stella (op. cit.) : seven and one-third
months.
Table II summarizes
the principal
data of anatomical
nature:
Affection of Side the pleura
I Left Costal pleura
TABLE
Pulmonary affection
II
Metastasis
II Right Costal, inter- Some subpleural
(Fig. 3) lobar and
bysmas
Lymph-glands liver-kidneys
diaphragmatic
suprarenals
pleura
III Left
Costal, media-
Bysmas on the
Lymph-glands
(Fig. 4) stinic and
hilum with pen-
liver
diaphragmatic
bronchial location
pleura
IV Left
Costal and
Parahilar
block
Right lung-
diaphragmatic pleura
extending
to
lower lobe
liver
V
Right
Costal, inter- Some subpleural
lobar and
bysmas
mediastinic
pleura
Lymph-glands
Histological Type
Cylindrical cells
Small undetermined cells
Adeno-carcinoma mucigenous (Fig. 5)
Cylindrical trabecular papillar (Fig. 6)
Small undetermined cells
(Fig.7)
cells
-
Leaving aside Case I, which was not anatomically
checked, but which
was clearly defined from an histological
aspect as result of biopsy (Fig. 2),
in all our other cases, there has always been evidence of a clear lack of
proportion
between the affection
of the pulmonary
parenchyma
by the
neoplastic
mass and its development
on the surface of the pleura.
In the lung, small or on occasion larger blocks of neoplastic
tissue have
been found in the vicinity of the hilum, in the form of plaques and bysmas
located between the broncho-vascular
formations
and sometimes
spreading
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818
BABOLINI
AND BLASI
March. 1956
towards the upper or lower lobes. In general there has been no evidence
of extensive
proliferation
inside the diameter
of the large bronchial
sec-
tions. Often, at this level, however,
the mucosa was found to be clearly
infiltrated.
In one of our subjects
(Case III) the neoplastic
tissue showed
immediately
after the parahilar
block, a clear tendency
to spread to the
peribronchial
area, wrapping
itself muff-like around the branches
of the
segmentary
bronchial
tubes.
In some other cases (II and V) large inter-parenchymal
blocks were
found only on the costa! side, and appeared
to be due to the direct spread
of the effusion on the pleura towards the lung.
This parenchymal
affection is always relatively
moderate
and in com-
parison, the spread of the tumor on the surface of the pleura has always
been found to be extensive.
Only in one case (IV) this occurred
in the
form of a large effusion which sealed together
the visceral and parietal
pleura and then wrapped
itself around the whole lung. This was par-
ticularly true on the costa! and mediastinic
areas. In other cases the two
leaves of the pleura remained
separated,
even though partially.
This
caused the creation of a cavity, which in some cases was large in size
(Cases II and III) and in some smaller (Case V). This cavity was lined
by thick neoplastic
layers-up
to a thickness
of one centimeter-which
formed on the visceral and parietal pleurae.
The possibility
that the neoplastic
invasion could proceed towards the
inter-lobar
pleura (Cases II and V), towards the mediastinal
pleura (Cases
III and V), and towards the diaphragmatic
areas (Cases II, III and IV),
was frequently
evidenced
in our cases, and had the usual characteristics.
Metastatic
affection of the lymph nodes of the hilum, of the lung, and of
FIGURE
3 (CAsE II): Right pleural space and collapsed
neoplastic
tissue over the surface of the costal pleura
diaphragmatic
surfaces.
lung stump; spreading and over the interlobar
of the and
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Vol. XXIX
PRIMARY
CANCER OF THE LUNG
319
the mediastinal
lymph nodes, although often formed by bysmas and festoons
of varying size, never assumed the character
of a massive invasion.
In
some cases indeed (IV) there was no macroscopic
evidence of an involve-
ment worthy of note.
In three cases-out
of the four on which anatomical
studies were made
-there was found to be a metastatic
focus of other organs: liver, three
times (Cases II, III, IV), kidneys and suprarenals,
once (Case II), contra-
FIGURE neoplastic
4 (CASE III): Left pleural space and collapsed
lung stump:
spreading
tissue over the surface of the costal and mediastinal
pleura.
of the
FIGURE
5 (CASE III): Histological
fragment
of the pleural
matous mucigen pattern on a thick collagen tissue.
surface:
adeno-carcino-
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320
BABOLINI
AND BLASI
March. 1956
lateral lung (Case IV), once.
With reference
to the cases studied
appearance
of the neoplasm.
In the
the pleural form of primary
cancer
any particular
histological
type. For
by us, Table first place it
of the lung this reason
II gives is clearly has no the cell
the histological
noticeable
that
predilection
for
structure
of the
substratum
may be formed by small undetermined
cells, or by cylindrical-
polymorphous
types, and indeed, by adeno-carcinomatose
structures
of a
mucigenous
nature. This is a general characteristic
of all the diverse ana-
tomical forms of primary
cancer of the lung
with one large nodule, or with multiple nodules)
(hilar infiltrative, and as is known
massive its histo-
logical nature may vary from case to case.
The epidermoid
or squamous
cell histological
type was not represented
in our cases. We certainly
do not know to what degree this exclusion
is
valid, but even in other case histories
(Botteri, Liberti and Stella) which
include the pleural form, no reference
is made to this latter oncotype.
From an histological
viewpoint
another aspect should be emphasized.
On the surface of the pleura the neoplastic
tissue is always associated
with a stromatic
collagenous
component
which is particularly
abundant,
and which attains even greater prevalence
than the quota of epithelial
cells. This basic tion of neoplastic of stasis in the
hyperplastic elements,
subpleural
reaction, is in part induced
and is partially
accentuated
lymphatic
network
(Scalfiio).
by the infiltraby phenomena The above re-
action sometimes
causes a considerable
alteration
in the arrangement
of
the infiltrated
cellular nests, which brings about a complete lack of con-
FIGURE 6A
FIGURE
6B
Figure 6A (CASE IV):
cal-cuboid
epithelium,
fragment:
same aspect,
Parenchymal
fragment:
neoplastic
tissue constituted
in a papillary
arrangenient.-Figure
6B (CASE
with a larger participation
of connective
stroma.
by cylindri4): Pleural
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Vol. XXIX
PRIMARY
CANCER OF THE LUNG
321
nection between the nature of heteroplastic
tissues in the lung and those
in the area of the pleura.
In this way, while in the lung there are varying types of arrangement,
such as islands and solid cords, or tubercular,
trabecular,
papillar, adeno-
matous, etc., in the pleural area there is more commonly found a scirrhous
type, with cellular formations
of varying density, in which solid forma-
tions in general predominate.
Of much greater rarity and of a barely
perceptible
type are trabecular
and papillar formations,
and those which
resemble glandular
formations
(See figures 6 and 7).
Although the factors considered
up to the present attribute
to the pleural
form of primary
cancer of the lung certain characteristics
which define
with considerable
clarity its clinical and anatomical
physiognomy,
they
do not explain the causes and conditions
which bring about the config-
uration of this complex structure.
The fact that it is not brought about
by single histological
substrate,
but that nearly all the cellular types of
broncho-alveolar
carcinoma
contribute
to its structure
makes it still more
difficult to determine
the effective morphogenetic
phases involved.
From the pattern of our cases and the examination
of the observations
of researchers
who have preceded
us, it seems possible to outline two
conditions
which are capable of giving rise to a surface development
of
primary tumor of the lung: Origin in subpleural
and absolutely
peripheral
parenchymal
sectors, and initial location in broncho-alveolar
sectors im-
mediately
adjacent to the mediastinal
pleura.
The attached
diagram
indicates
this double possibility
which in all
FIGURE
7A
FIGURE
Figure 7A (CASE V): Parenchymal
fragment:
neoplastic
tissue
cell cancer.-Figure
78 (CAsE V): Pleural fragment: nests of
background of a thick collagen tissue.
7B
of the neoplastic
kind of small. cells on the
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322
BABOLINI
AND BLASI
March. 1956
probability
is to be considered
linked to the adjacency
of heteroplastic
tissue of neoplasm to the pleural lymphatic
network;
this also leads one
to believe that even in the first hypothesis
the conditions
which favor
surface development
may be given by propagation
in a direct sense of
the lymphatic
stream;
in the second hypothesis
one finds a retrograde
tendency,
which also appears
to lead to an extensive
affection
of the
pleural covering.
Far from being explanatory,
this statement
is only a determination
of
the circumstances
which bring about the anatomical
picture in question.
As in each individual
sector of general and specialized
oncology, there
are numerous
obscure points which the information
and knowledge
in our
possession
at present are insufficient
to clarify.
SUMMARY
The pleural form of the primary
cancer of the lung constitutes
an in-
frequent,
but absolutely
particular
type among the neoplastic
lung pro-
cesses. Its chief characteristic
is that the neoplastic
tissue, instead of
involving
the depth of the parenchyma
of the lung, is almost entirely
spread upon the pleural surface, becoming very similar to primary cancer
of the pleura.
The histological
analysis
allows to differentiate
it by finding cellular
elements of broncho-alveolar
derivations.
The authors
have collected
five cases of the pleural form out of a
total group of 82 cases of primary
cancer of the lung: in one of these a
biopsy through pleuroscopy
established
the right diagnosis.
La forma pleura del cancer
frecuente,
pero muy peculiar
RESUMEN
primitivo
del pulm#{243}n constituye
un tipo poco
entre los procesos neopl#{225}sicos pulmonares.
FIGURE primary
8: Scheme lung cancer.
/
of possible
morphogenetic
derivations
of the pleural
form of
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Vol. XXIX
PRIMARY CANCER OF THE LUNG
323
Su caracterIstica
principal
es que en lugar de invadir Ia profundidad
del
par#{233}nquima pulmonar
se extiende casi completamente
sobre la superficie
pleural haci#{233}ndose muy semejante
al cancer primario
de la pleura.
El an#{225}lisis histol#{243}gico permite diferenciarlo
al encontrar
los elemontos
celulares de las derivaciones
broncoalveolares.
Los autores han reunido cinco casos de la forma pleural de un total de
82 casos de cancer pulmonar;
en uno de estos una biopsia a trav#{233}sde Ia
pleuroscopla
estableci#{243} el diagn#{243}stico correcto.
RESUME
La forme pleurale du cancer primitif du poumon constitue
habitue! mais tout a fait particulier
des n#{233}oplasies pulmonaires.
un type peu Sa carac-
t#{233}ristique majeurs est que le tissu n#{233}oplasique au lieu de se d#{233}velopper dans
la profondeur
du parenchyme
du poumon
surface pleurale, devenant tr#{232}sesmblable
s'#{233}tendpresque en totalit#{233} sur la
a un cancer primitif de la pl#{232}vre.
L'analyse
histologique
permet de la diff#{233}rencier par la constatation
d'#{233}l#{233}mecnetlslulaires
d'origine broncho-alv#{233}olaire.
Les auteurs ont recueilli cinq cas de forme pleurale sur un groupe total
de 82 cas de cancers primitifs
du poumon:
dans l'un d'eux une pleuroscopie
avec biopsie permit d'#{233}tablir le diagnostic
correct.
ZUSAMMENFASSUNG
Die pleurale Form des prim#{228}ren Lungenkarzinoms
stellt einen seltenen,
aber durchaus
besonderen
Typ unter den Lungenneoplasmen
dar. Das
Hauptkennzeichen
dieser Art von Karzinom
ist die fast ausschliessliche
Ausbreitung
neoplastischen
Gewebes auf die pleurale Oberfi#{228}che an Stelle
des Vordringens
in die Tiefe des Lungenparenchyms.
Somit wird dieser
Krebs dem prim#{228}ren Pleurakarzinom
sehr #{228}hnlich.
Die Differenzierung
ist durch die histologische
Untersuchung
moglich,
indem zellulare Elemente
broncho-alveol#{228}ren
Ursprungs
bei dieser Tumor-
Art nachgewiesen
werden k#{246}nnen.
Die Verfasser
haben 5 F#{228}lleder pleuralen
Form unter insgesamt
82
Fallen von prim#{228}rem Lungenkarzinom
gesammelt;
in einem Fall wurde
die richtige
Diagnose
durch thorakoskopische
Probe-Excision
gesteilt.
REFERENCES
1 Verga, P. and Botteni, G.: "Il carcinoma
primitivo
del polmone,"
Cappelli Ed.,
Bologna,
1931.
2 Roussy, G. and Huguenin,
R.: "Essai de classification
anatomo-clinique
des cancers
primitifs
du poumon,"
Ann. Anatom.
Pathologique,
5:7, 1928.
3 Olmer, D., Olmer, G. and Roume, H.: (Quoted by Liberti e Stella), Marseille
Med.,
7:328, 1938.
4 Liberti, R. and Stella, G.: "II cancro primitivo del polmone," Ed. E.A.T., Napoli,
1949.
5 Eizaguirre,
E.: "El Cancer Broncopu1monar,"
Ed. Paz Montalvo,
Madrid, 1952.
6 Stival, L.: "La neoplasia
pnimitiva
polmonare:
rapporti
tra tipo istologico,
sede
e gli altri principali
caratteri,"
7 Dell'Acqua,
G.: "Mesotelioma
Biologica
Latina, 4:212, 1951.
della pleura, Atti 51#{176C},ongre88o
Med. mt., p. 220,
8 Frissel,
L. F. and Knox, L. C.: "Primary
Carcinoma
of the Lung," Am. Jour,
Cancer, 30:219, 1937.
9 King, D. S.: "Primary
Cancer of Lung," New England Jour. Med., 219:828, 1938.
10 Scalfi, G.: "Istogenesi
e classazione
dei tumori maligni
primitivi
della pleura,"
Boll. Soc. Med. Chirurg. di Pavia, 65:1, 1951.
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The Pleural Form of Primary Cancer of the Lung G. BABOLINI and A. BLASI Dis Chest 1956;29; 314-323 DOI 10.1378/chest.29.3.314
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