DIFFUSE PRIMARY ALVEOLAR CARCINOMA OF THE LUNG
(SO-CALLED "ALVEOLAR C E L L " TUMOR OF LUNG)*
MORRIS A. SIMON, M.D.
From the Department of Laboratories, Jewish General Hospital, Montreal, Quebec
In recent years numerous reports have been published of a unique type of
primary lung tumor occurring in man. These tumors are characterized by an
unusual type of nonciliated, tall, columnar and questionably mucus-secreting
cells which line and are loosely attached to apparently unaltered alveolar walls,
show papillary formation within alveoli and frequently desquamate into the
alveoli. The tumors occur almost invariably in both lungs. About one-half of
the tumors are found localized to the lungs at the time of death, often without
evidence of lymphatic invasion, and the remainder show either local or distant
metastases. None of the tumors shows the ordinarily accepted and classic
features of primary bronchiogenic carcinoma, such as invasion of bronchial wall
with or without stenosis or ulceration and/or atelectasis. Similarly, no primary
tumor in any other situation is found so that metastatic tumor can be definitely
ruled out. Finally, in almost all instances, the point of origin, whether from
bronchiolar basilar epithelium, infundibular epithelium, or from lining alveolar
cells remains a mystery or, at least, is controversial.
To this tumor a variety of names has been given. Thus Lohlein13 called it
"cystic papillary lung tumor", Bonne4 introduced the name of "pulmonary
adenomatosis", Taft and Nickerson20 preferred "mucous epithelial hyperplasia
of lungs" and finally the term "alveolar cell tumor of lungs" was suggested by
Neubuerger and Geever.18 The term "diffuse primary alveolar carcinoma of
lung" is here used for reasons to be discussed.
The diagnosis of this type of tumor has only been made post mortem in all
instances, except by Wood and Pierson.27 In their case, the diagnosis was made
on surgical material removed at operation. Lobectomy was performed but
circumstances subsequently proved that the lesion was diffuse and bilateral.
As far as the author is aware, no clinical diagnosis without recourse to examination of tissue has ever been made. As will be demonstrated, however, it is
possible to make the diagnosis ante mortem by biopsy of tissue aspirated from the
lung. In the case to be reported, the clinical diagnosis of diffuse alveolar carcinoma of the lung was suspected and discussed, but was not clinically made.
In retrospect, the biopsy of aspirated tissue was clearly diagnostic, but a definitive diagnosis was not made, in spite of the author's experience with a previously
reported case.22
REPORT OF CASE
Clinical Data
The patient was a 39 year old man who was first admitted to this hospital, March 5,
1946, in the service of Dr. David Mendel. At this time his complaints were chest cold and
* Received for publication, June 18, 1947.
783
784
SIMON
cough of six weeks' duration, blood-tinged sputum, general malaise, fever and vague pain of
twenty-four hours' duration.
Past illness. In November 1931, he was admitted to the Royal Victoria Hospital because
of dizziness, loss of consciousness, hematemesis and melena, but no cause for the gastrointestinal bleeding was discovered at that time. In December 1934, he was again admitted
to the Royal Victoria Hospital with a history of melena which had recurred six or seven
times since 1931, the last time in August 1934. As on the previous examination, no evidence of disease of the gastro-intestinal tract was found. He was then well until September
1944, when, while working in Vancouver, B. C , he became very weak one morning and
passed a black, tarry stool. He was treated in the Emergency Clinic of the Vancouver
General Hospital and discharged the same day. He had no further hematemesis or melena.
In May 1945, the patient caught a chest cold and complained of severe pain in the left side
of the chest accompanied by cough and sputum. X-ray films of his chest revealed a lesion
which was suspected of being tuberculous and he was admitted to the Tranquille Sanatorium
in Vancouver for nine weeks. Here, repeated examinations of sputum and guinea pig inoculations were negative for tubercle bacilli. An x-ray film taken May 6, 1945 revealed
"light infiltration within the second and third interspaces and dense, soft-looking infiltration in the lower hilar area extending to the mid-lung zone on the right and light
mixed infiltration in the fourth interspace on the left". He was treated with sulfadiazine
and admitted to the Vancouver General Hospital on July 10, 1945. After thirteen days in
the hospital, he was discharged with a diagnosis of long-standing pneumonitis.
Present illness. The patient remained in Vancouver until January 1946 when he contracted "flu". The cough continued and he returned to Montreal late in February. He
was told by a physician that he had pneumonia and was admitted to this hospital on March
5. On the previous day he had noted that his sputum was tinged red.
Physical examination revealed a moderately well nourished individual lying comfortably
in bed. On admission, his temperature was 99.8 F., pulse rate 85 per minute and respiratory rate 20 per minute. The physical findings in the chest were compatible with those
of consolidation and pleural effusion on the left side. X-ray films of the chest on March 7,
two days after admission, showed large areas of consolidation in the right upper lobe and in
the right and left mid-lung fields.
The patient remained in the hospital from March 5 to June 15. During this time, his
condition was thoroughly investigated. Repeated x-ray examinations of the lungs showed
areas of consolidation in both lung fields which at times seemed to diminish in size. X-ray
films of the gastro-intestinal tract and urinary tract failed to reveal evidence of disease.
White blood cell counts varied from 7600 to 23,700 per cu. mm. and the sedimentation time
was increased. Repeated examinations of sputum for tubercle bacilli and fungi of various
types were negative. The patient's temperature fluctuated irregularly between 98 F.
and 103.6 F. and he was given large amounts of penicillin with indifferent results. Bronchoscopic examination on March 16 was negative. Biopsy of material aspirated from the
lungs on May 9 revealed a few atypical cells. The diagnosis stated: "The possibility of
tumor cells cannot be excluded."
The clinical diagnosis during this period of the patient's hospitalization was in doubt, the
possibilities of fungus infection of the lung and of Boeck's sarcoid having been considered.
The patient was discharged on June 15 after 102 days in the hospital with a diagnosis of
"chronic lung disease, etiology unknown".
He was re-admitted to the hospital on August 15, 1946. During the preceding two
months, he worked occasionally, but continued to have weakness, cough and vague pains in
the chest. About July 15, he noticed increased shortness of breath and a week later expectorated blood-tinged sputum and developed chills, fever and sweats. These symptoms
became progressively worse until re-admission to the hospital.
Physical examination again revealed irregular signs of consolidation in both sides of the
chest. His leukocyte count on admission was 22,500, his pulse rate was 115 per minute,
respiratory rate 20 per minute and temperature 102 F. He was critically ill and the tern-
ALVEOLAR CARCINOMA OF LUNG
785
perature swung irregularly from 98 F. to 104.5 F. Repeated x-ray films at this time and
throughout this hospital admission revealed evidence of consolidation of both lung fields.
These areas appeared to vary in size and shape from time to time, occasionally increasing
and sometimes diminishing in size. Clinically, no definite diagnosis could be established.
On August 21 a lung puncture was performed and the following report was made from
examination of a microscopic section of the aspirated material (Fig. 2): "Atypical epithelial
cells, probably tumor cells. Papillary masses of glandular epithelial cells in the tissue
section strongly suggest a tumor of adenomatous type."
Another lung puncture on September 4, failed to reveal the presence of tumor cells.
After twenty-six days of fever, the patient's temperature became normal. Numerous examinations of sputum and aspirated lung material for fungi were negative. Type III
Pneumococcus was recovered from a lung puncture on one occasion. His white blood cell
count dropped to 8900 per cu. mm. and penicillin was discontinued. The patient was discharged, slightly improved on October 29, seventy-four days after admission with a clinical
diagnosis of chronic and organizing interstitial pneumonitis. It was during this admission
that the possibility of a diagnosis of diffuse alveolar carcinoma was considered. During this
hospitalization Dr. N. Freedman also reported the presence of peculiar cells in the sputum.
These were large, oval cells and were unlike any he had ever seen before in sputum. The
cells were shown to Dr. George Papanicolaou who could not identify them but considered
them to be tumor cells.
Nine weeks later, on January 3, 1947, the patient was re-admitted to this hospital for the
third and last time. During the preceding four weeks his cough had increased in frequency
and blood-streaking of sputum had become more frequent. He developed attacks of unconsciousness with deviation of the eyes and intermittent attacks of severe headaches.
Six days before admission weakness of the left foot and leg were noted. Physical examination at this time again revealed signs of irregular consolidation in both lungs and a hemiparesis involving the left side of the body.
X-ray findings were essentially the same as previously reported. On neurologic consultation, it was suggested that there was a lesion of indeterminate type in the right cerebral cortex. The patient had a number of epileptiform seizures while in the hospital. His
condition deteriorated rapidly and a sputum examination on January 7, revealed cells which
could not be excluded as tumor cells. He died on January 26, twenty-three days after his
last admission. Although- numerous conditions were considered, including pulmonary
adenomatosis, no definite clinical diagnosis was established.
Macroscopic Postmortem Findings
Autopsy was performed sixteen hours after death.
The right pleural cavity was completely obliterated by dense, sheetlike, firm adhesions
which bound the lungs on all aspects to adjacent structures including the pericardial sac
and diaphragm. The right lung was voluminous and within it irregular and indefinite
masses could be palpated. The lung had a rubbery consistency and at the apex a few
emphysematous areas were present.
A few dense, sheetlike adhesions bound the left lung to the lateral chest wall. Dense
adhesions also bound this lung to the diaphragm and pericardial sac. Where adhesions
were not present, the pleural surfaces were smooth and of a mottled violet and gray color.
Within the lung, which was emphysematous, irregular and indefinite rubbery masses could
be palpated in both lobes. The right lung weighed 1670 gm. and the left 1450 gm.
Multiple sections through the lobes of the right lung revealed cut surfaces that were
largely replaced by pinkish gray, finely granular, gelatinous and translucent tumor masses
(Fig. 1). These tumor masses varied from 0.3 to 3.5 cm. in diameter. The edges were poorly
defined and the tumor appeared to merge insensibly into the adjacent lung parenchyma.
These nodules were raised slightly above the general level of the lung. Some were discrete, others had coalesced and, when scraped, showed a glairy, gelatinous and sticky material on the knife. In some places in the intervening lung tissue between the tumor masses
786
SIMON
FIG. 1. Right lung showing nodular, diffuse character of
tumor. The cut surface presents a sticky, gelatinous appearance. Print from a colored lantern slide.
FIG. 2 Material aspirated from lung during patient's second hospitalization,
lnis is a fragment of lung with alveoli lined by tall, columnar, epithelial tumor cells
showing papillary infolding. Hematoxylin and eosin. X 185.
dilated alveoli could easily be seen with the naked eye. These changes were present in all
lobes of both lungs with variation only in the size and configuration of the tumor nodules
and in the degree of emphysema and hyperemia of the intervening lung.
ALVEOLAR CARCINOMA OF LUNG
787
Sections through the trachea and major bronchi revealed a pink, velvety and intact
mucous membrane. The terminal portions of the bronchi in the lower lobes were slightly
dilated and contained reddish brown, mucoid material. Careful search in the multiple
bronchi examined failed to reveal any ulcerating or stenosing lesion which might suggest a
primary bronchiogenic tumor.
The paratracheal, mediastinal and peribronchial lymph nodes were distinctly enlarged
and measured up to 2.5 cm. in diameter. On section, they presented moist, mottled gray
and black, homogeneous surfaces with no gross evidence of tumor.
Painstaking search of all other thoracic and abdominal viscera failed to reveal gross
evidence of any tumor. No lesions were found in the gastro-intestinal tract to explain the
patient's previous melena (1931 to 1944).
The right cerebral hemisphere of the brain was larger than the left. In the precentral
region of the vertex of the right cerebral hemisphere and extending along the median
fissure was a sharply demarcated area of diminished consistency which measured approximately 5.0 cm. in greatest diameter. A similar less sharply defined area was present in the
percentral region at the vertex on the left side. Coronal sections of brain (Fig. 4) revealed
these two areas to be more or less cystic or honey-combed in appearance and some of the
cysts were filled with colorless, gelatinous material. A third metastasis was present in the
right cerebral hemisphere, more caudad and at the level of the pons.
Microscopic Findings
Many blocks were taken from every lobe of the lungs to include obvious
tumor, peripheral portions of tumor and grossly uninvolved pulmonary tissue.
The histologic changes were essentially similar in all areas except in the firmer
masses where considerable interstitial fibrosis of the lung was noted microscopically.
Throughout all sections, large areas were encountered where thin-walled,
slightly dilated alveoli were lined by single and, at times, pseudostratified layers
of tall, columnar epithelial cells. These cells were loosely attached to apparently
unaltered alveolar walls and in many places were detached in small strips or
sheets and lay free within alveoli or were attached to the alveolar wall only at
one end of the strip. Papillary infolding into alveoli was commonly observed.
The lining cells showed basally arranged, uniform, oval nuclei composed of
finely granular chromatin. Moderate numbers of nuclei showed rather prominent
nucleoli but this was not a constant feature (Fig. 5). Only rarely was a mitotic
figure seen. The tumor cells showed abundant pale pink-staining cytoplasm and
many of the cells contained "goblets". From these "goblets" small amounts of
pale mucoid material extruded and was found free within alveoli. This mucoid
material stained pink with hematoxylin and eosin. In our hands Best's
mucicarmine stain gave indeterminate results and with the Masson trichrome
stain the mucoid material stained a pale blue. The tumor cells showed no cilia
but a fine "brush border" was noted in the better preserved cells.
Many alveoli were found filled with desquamated tumor cells and, in some
alveoli, large, pale, circular cells were seen showing finely vacuolated cytoplasm
and relatively small compact nuclei. Transitional forms between obvious
desquamated tumor cells and these phagocytic cells were noted. Fields were
encountered in which only rare alveoli were lined by a few desquamated tumor
cells and here the majority of the alveoli contained fairly large numbers of lym-
788
SIMON
L
° T P ° w e l \ v i e w of lung. Note large area of organized interstitial pneum ^ P o ' ?'
monia lower left containing residual alveoli lined by tumor cells The diffuse nature
eosin
X025mVOlVlngt h e
alVe
°U "
S6en a b
°Ut
the a
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HematoxyHn and
ytes and occasional polymorphonuclear leukocytes. No fibrin or bacteria
noted. Cultures from these lungs at autopsy were sterile.
ALVEOLAE CARCINOMA OF LTJNG
789
FIG. 4. Coronal sections of brain showing metastases. Note the large cystic
areasfilledwith clear, mucoid material.
In all lobes except the right lower lobe, extensive irregular areas of fibrosis
were encountered. These areas (Fig. 3) were composed of compact and relatively cellular connective tissue within which were encountered a few irregular
spaces lined by cells somewhat shorter than those lining the unaltered alveoli.
790
SIMON
The lining cells in these areas were regular in appearance and basement membranes were sharply defined. The general impression gained from such areas
was that these spaces represented residual alveoli in foci of organized interstitial
pneumonitis. In the periphery of these areas of fibrosis the alveolar walls
appeared to be unaltered and here alveoli were lined and partly filled by typical
tall columnar epithelial tumor cells.
Throughout all sections painstaking search failed to reveal any identifiable
bronchioles which were lined by similar tall tumor cells. Wherever bronchioles
were identified stratified cuboidal cells were present differing in no respects
from those usually found. In all sections nothing was seen that could be identified as lymphatic or blood-vascular invasion.
Sections through multiple hilar and mediastinal lymph nodes failed to reveal
microscopic evidence of metastatic tumor.
Sections taken from the region of the cystic areas in the cerebral hemispheres
(Fig. 6) showed extensive replacement and destruction of brain tissue by tumor
identical to that described in the lungs. Here large cystic dilated spaces were
seen lined by simple and pseudostratified, nonciliated columnar epithelium
showing papillary infolding. Into some of these cystic spaces desquamation of
lining cells had occurred and, within these spaces, spherical cells with vacuolated
cytoplasm and eccentric nuclei similar to those found within alveoli were noted.
Many of the spaces contained pink-staining, stringy mucoid material identical
with that seen in the alveoli lined by tumor cells. Adjacent to the tumor which
invaded the cortex and subjacent white matter, there was extensive destruction
of brain tissue with compound fat granule cells and microglial cells present in
large numbers. The tumor extended into the leptomeninges where the cysts
appeared to be larger than elsewhere.
Sections taken through all other organs failed to show microscopic evidence
of tumor.
Anatomic Diagnoses
Diffuse primary alveolar carcinoma of the lungs, bilateral, with metastases
to brain; organizing interstitial pneumonitis, bilateral; bronchopneumonia,
bilateral.
DISCUSSION
Diffuse primary alveolar carcinoma of the lungs may present two distinctly
different gross pictures. In one form, the gross picture may be indistinguishable
from lobar pneumonia in the state of so-called gray hepatization. Here the
FIG. 5. Medium-powered section of lung to show character of lining cells, unaltered
alveolar walls and brush border of cells. Note detachment of cells in alveolus to left of
center and desquamated cells in alveolus in upper and lower left corners. Goblet formation
can also be seen in many cells. Hematoxylin and eosin. X 200.
FIG. 6. Metastasis in brain. Note that the cells lining the acini are identical with
those seen in the lung with the same tendencies to papillary formation, desquamation and
mucoid production. Note compound fat granules, lower left. Hematoxylin and eosin.
X 93.
2flr 5
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791
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792
SIMON
lung is gray and consolidated but may present a sticky, mucoid substance on cut
surface. In a previously reported case22 which was of "pneumonic" type,
Friedlander's bacillus was recovered. Taft and Nickerson26 have likened the
cut surfaces of the lungs of diffuse primary alveolar carcinoma to Friedlander's
pneumonia. In the present case, Type I I I Pneumococcus was recovered
during life.
In the second form, the lungs of diffuse primary alveolar carcinoma may
present a nodular appearance similar to that in the present case (Fig. 1). In
this form, the cut surface shows numerous large and small, poorly defined,
elevated, pinkish gray masses which blend imperceptibly with the surrounding
lung tissue. The surfaces of these nodules are, at times, finely granular :md are
covered with a sticky, mucoid material and the intervening lung tissue shows
variable degrees of hyperemia. These nodules may be rubbery in consistency
and the intervening lung shows variable degrees of crepitation depending on the
amount of emphysema and/or pneumonia present. In this connection it may
be pointed out that a pneumonia of variable degree always accompanies diffuse
primary alveolar carcinoma of the lungs and may be of lobar type as in the case
of Alexander and Chu.1 In some cases variable amounts of organized interstitial pneumonitis may be the residua of former pneumonic processes.
Microscopically, the picture is characteristic. Alveoli, the walls of which
are apparently unaltered, are lined by delicately attached, single, or pseudostratified layers of tall, columnar epithelial cells many of which show papillary
infolding into the alveoli. These cells are regular in appearance, size and staining
quality with basally arranged oval nuclei. The nuclei show finely granular
chromatin, occasional nucleoli and, only rarely, is a mitotic figure encountered.
The lining cells frequently show "goblet" formation and produce a type of
secretion which we have found does not stain readily with Best's muciearmine
stain. Alexander and Chu 1 stated they were able to stain the mucinous material
by this method and Taft and Nickerson26 mentioned mucus which stained with
"aniline dyes". In any event, an evident mucoid material appears to be secreted
by these cells and may also be found in the alveoli. The tumor cells are not
ciliated but may show a fine "brush border" at the free edge. The lining cells
desquamate as single cells or sheets of cells into the alveoli where they may
assume circular forms. At times, it appears that the large, pale phagocytic
cells seen in many of the alveoli are altered desquamated tumor cells. These
lining cells in no situation appear to be continuous with recognizable lining
bronchiolar cells either in random or serial sections.
The distribution of these lining cells is quite irregular. Some microscopic
fields show all alveoli to be lined by tumor cells and other fields reveal no alveoli
thus lined. All lobes of the lungs are involved in variable degree. In some
instances, where interstitial fibrosis is found in the lungs as the result of organizing pneumonitis, numerous spaces, probably residual alveoli, are found lined
by tumor cells (Fig. 3).
Lymphatic invasion is rarely observed and blood vascular invasion is even
more rare. These must occur, however, in order to explain the metastases.
ALVEOLAR CARCINOMA OF LUNG
793
In the larger group of so-called "alveolar cell tumors of the lungs" collected
by Neubuerger and Geever18 the lining cells have been shown to vary from high
cuboidal to columnar and much anisocytosis and considerable degrees of anaplasia have been noted. In their collected cases no communication or continuity
between lining cells and bronchiolar epithelium has been established.
Histogenesis
First and foremost, in this case as in almost all other similar cases reported
in the literature, the ordinary criteria suggesting a primary bronchial origin
were absent. (Ikeda's12 case No. 2 showed a gross bronchial tumor and therefore
is probably unacceptable as an example of the type of tumor under discussion.)
There was no gross or microscopic invasion of bronchial wall either with or without
stenosis or ulceration and no associated atelectasis was present. Indeed, the
character and appearance of the cells lining the alveoli in cases of diffuse primary
alveolar carcinoma are so unlike the ordinary bronchiogenic carcinomas as to
suggest at once that the tumors are different. The lining of unaltered alveolar
walls by these loosely attached cells in ordinary bronchiogenic carcinoma (if it
exists) certainly must be most unusual.
Are these tumors in the lung metastatic in origin? To this question a categorical negative answer can be given. In almost all the cases reported in the
literature, as in the present case, no primary tumor was found other than in the
lungs. Since there are now about 70 recorded cases it seems extremely unlikely
that more than 60 pathologists would all miss a primary tumor in a situation
other than the lung. It must be admitted, however, that occasionally a
metastatic carcinoma may assume an intra-alveolar arrangement not unlike
that presented here. This is an exception rather than the rule and does not
appear to deserve the emphasis placed upon it by Herbut. 11
Herbut 11 has also suggested that these tumors arise from bronchiolar epithelium
particularly in foci of bronchiectasis. This concept cannot be substantiated by
actual gross or microscopic examinations. In the first place, bronchiectasis in
diffuse alveolar carcinoma of the lungs is an extremely infrequent and inconstant
accompanying condition. Numerous cases of diffuse alveolar carcinoma have
been reported in which the lesion has been bilateral and has showed no evidence
of lymphatic invasion or lymph node metastases. Under these circumstances,
if Herbut11 is correct, bilateral and diffuse bronchiectasis should be of frequent
occurrence in this condition. The supposition that the tumor may start in one
focus and then by continuity line pre-formed spaces such as the alveoli in widely
separated portions of the lung without in some places lining bronchioles or bronchi
seems untenable unless one assumes implantation by aspiration. In microscopic
sections it has been impossible to demonstrate direct continuity either in random
or serial sections between bronchiolar epithelium and tumor cells lining the alveoli. Furthermore, the cells lining bronchioles are quite different from the tumor cells, none of which ever shows cilia. For these reasons it appears unlikely,
no matter how tempting the concept, that the tumor cells arise from bronchiolar
lining cells.
794
SIMON
The inability to demonstrate that these tumors arise from bronchiolar lining
cells immediately raises the controversial question as to whether epithelial alveolar lining cells exist, and if so, whether tumors may arise from these cells.
Such histologists as Bensley and Bensley,8 Miller,16 and Cooper6 are of the opinion
that a continuous layer of epithelial cells lines the alveoli. Maximow and Bloom,15
Rose,20 Fried, 8 and Loosli14 believe that the lining cells are mesenchymal. Ross21
believes that both mesenchymal and epithelial cells may line alveoli. It is difficult to imagine that the lung which is a diverticulum of the primitive gut should
differ from other evaginations, all of which are lined throughout with epithelium.
Bell2 and Geever, Neubuerger and Davis 9 studied the lung as affected by
chronic passive hyperemia and by inflammatory conditions. They observed
what they considered to be epithelial proliferation from alveolar lining cells.
Hence, it was their opinion that alveolar lining cells may give rise to tumors.
Ikeda12 and Simonds and Curtis23 have produced alveolar epithelialization in experimental animals by the use of oily substances and of coal tar. Murphy and
Sturm17 and, more recently, Grady and Stewart10 have induced multiple adenomatous tumors originating along alveolar walls of the lungs of mice, and Slye,
Holmes and Wells26 have reported spontaneous, primary, adenomatous tumors
of this type in the lungs of mice. The disease known as jagziekte, epizootic
adenomatosis, or verminous pneumonia, an infectious endemic disease of sheep,
the virus of which was recently isolated by Dungal, 7 is regarded as an adenomatous hyperplasia of the alveolar epithelium by Cowdry and Marsh. 6
The experiments and observations quoted immediately above strongly suggest
that alveolar epithelium does exist and that under proper circumstances may
proliferate and may, indeed, give rise to tumors. The fact that cases have been
described in which the tumor was localized to the lungs without gross or microscopic evidence of lymphatic invasion tends to support the concept of a multicentric origin of this type of tumor.
Because of the controversy concerning the existence of epithelial alveolar lining
cells, considerable confusion in the nomenclature of this tumor has arisen in the
literature. Neubuerger and Geever18 chose the name "alveolar cell tumor" without intending to connote the histologic origin of the cell. If the word "cell"
is omitted and the condition described as "diffuse primary alveolar carcinoma of
the lungs", definitive reference as to possible cell origin {e.g., bronchial, infundibular or alveolar) is omitted in this perplexing subject. Similarly, the terms
"pulmonary adenomatosis" and "mucous epithelial hyperplasias of the lung" are
misleading for, in spite of the benign appearance of some of these tumors histologically and, particularly when they are, as yet, confined to the lungs, this
tumor should be regarded as a slow-growing but eventually metastasizing carcinoma. Invariably there is a considerable degree of pneumonia associated with
these tumors and it may well be that the degree of pneumonia frequently is the
cause of death before metastases have had time to develop.
The etiology of diffuse primary alveolar carcinoma of the lungs in man is unknown. From sheep affected with jagziekte, Dungal 7 isolated a virus which produces a strikingly similar lesion in the lungs of these animals. This virus does
ALVEOLAR CARCINOMA OF LUNG
795
not appear to be pathogenic for man as shepherds who are housed for long periods with these sick animals do not contract the disease. Attempts to transmit
the disease to various laboratory animals with human autopsy material by Richardson,19 Sims,24 and Wood and Pierson27 have been uniformly unsuccessful.
The clinical course and clinical findings in diffuse primary alveolar carcinoma
of the lungs are not sufficiently clear-cut to permit an unequivocal clinical diagnosis. Cough, x-ray evidence of bilateral lung consolidation which varies in size
from time to time, absence of eosinophilia (Loeffler's syndrome should be excluded), with or without hemoptysis and the progressive nature of the disease,
are suggestive features. The diagnosis, however, can be established during the
life of the patient on the basis of biopsy of material aspirated from the lung.
In this case the diagnosis should have been established on the basis of such a
biopsy (Fig. 2).
SUMMARY
A case has been presented of diffuse primary alveolar carcinoma of the lungs
with metastases to the brain. This disease .has also been called "pulmonary
adenomatosis", "mucous epithelial hyperplasia of the lungs" and "alveolar cell
tumor of the lungs". Although controversial, the evidence suggests that this
tumor is multicentric in origin and is probably derived from lining alveolar epithelial cells. Clinically, the signs and symptoms of this disease are not sufficiently characteristic to permit a correct diagnosis but a correct diagnosis can
be established during the life of the patient on the basis of biopsy of material
aspirated from the lung.
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