Malignant Mixed Tumor of the Lung

84

VADILLO-BRICENO, FEDER AND ALBORES-SAAVEDRA

occasional doses of 75 mg of Demerol for pain. Later medications included

glutethirnide

(Doriden)

and phenobarbital

at

bedtime, dextropropoxyphene (Darvon) for headache, and 400 mg of nieprobaniate three times a day. After discharge the patient was observed in the hospital clinic with normal progression of her pregnancy and subsequent fetal electrocardiograms showed normal fetal cardiac activity.

Her final admission, to the obstetrical sen’ice, was on September 28, 1967, after mild chest pain, moderate tightness of the chest and numbness of the left arm had persisted for ten to twelve hours. Examination on entry revealed no significant change from previous examinations done at the clinic; the utenis was seven centimeters above the umbilicus.

Serial electrocardiograms revealed no significant change from previous records; enzymes were within normal limits. The patient received oxygen and Demerol as needed, and was not in active labor. She complained a few times of chest pain hut her vital signs remained unremarkable with the exception of mild sinus tachycardia with the rate of 110 a minute. It was decided to keep her in the hospital until labor ensued, but she was not monitored. On October 8, 1967, at 4:30 AM, she was helped by a nurse to the bathroom, and her return to bed was uneventful; but at 5:30 AM she was lou nil dead in bed.

Autopry

Report Generalized atherosclerosis, moderate; arteriosclerotic heart disease manifest by (1) coronary atherosclerosis,

induce uterine contractions. Retrospective analysis of the case developed the feeling that continuous monitoring should have been employed

and might have at least spared the

life of the infant. Incidentally,

the timing of a in relation to the T wave (vulnerable zone) in producing an arrhythmia is demonstrated in the tracing (Fig 2). premature

ventricular

contraction

REFERENCES

1 Vogel

J,

Pryor R and Blount SC, JR: Direct current

defibrillation during pregnancy, JAMA, 193:70. 1965 2 Meitu

M Fetal electrocardiography

svith direct current countershock,

and

cardioversion

Dix Chest, 4S:324, 1985

3 Sussman, H: Atrial flutter with 1:1 A-V conduction successfully treated with DC shock, Dix Chest, 49:99, 1986

Reprint requests: Dr. Curry, 9801 Georgia Avenue, Silver Springs, Maryland 20902.

MalignantMixed Tumor ofthe Lung* Frn,mcicu Vi,dillo-Brie#{241}o,M.D.,” William Feder, M.D., and Jorge Aibores-Saaoedra, .U.D.t

severe, (2) thrombotic occlusion of circumflex branch of left coronary artery, (3) acute posterolateral myocardial infarction, (4) old posterolateral myocardial infarction; intrauterine pregnancy at term: normal, 6 lb 14 oz female fetus.

DiscussioN Electroversions of cardiac arrhythrnias comnplicating heart surgery during pregnancy have been reported. In one instance, the arrhythmia was atrial fibrillation’ and in#{149} another, atrial ilutter.23 j Lown’s experience with nearly 800 patients undergoing eleetroversion for arrhythmias, two were pregnant (personal communication). In most of these cases only small amounts of electrical dis-

charge were employed and the fetal heart was not monitored. In our case with a life threatening arrhythmia a large electrical discharge of 300 wattseconds was used and the fetal heart monitor revealed no disturbance of rhythm or rate (Table 1) The possibility

of producing

iatrogenic

fetal ar-

rhythmias or the onset of uterine contractions has been considered. Monitoring of the fetal heart beat is essential for the early detection of fetal cardiac arrhythmia. Whether countershock could be applied is not known. If the pregnancy is advanced, as in our case, the possibility of cesarean section should be kept in mind and close cooperation with the obstetrical department is important. The precordial delivery of 300 watt-seconds discharge in our patient did not alter the fetal electrocardiogram or

A malignant mixed tumor of the lung occurring in a 67year-old man is presented.Clinical and autopsy findings are described. By chest roentgenograms Irregular caleffic deposits within a large rounded pulmonary mass were demonstrated and considered to be an Important dingnoslic feature Crossly the primary tumor was large, rounded with well-defined borders and calcified and noncalcified cartilaginous nodules distributed at random, Microscopically it was composed of a mixture of three different carcinomatous components (small cell undifferentiated, epidermoid and adenocarcinoma) and several mesenchymal tissues (cartilage, adipose and myxoid tissues). These latter were well differentiated and were found only In the primary tumor; their origin is unknown. The differential diagnosis with teratomas and carcinosarcomas of the lung is discussed. similar to those of the salivary glands have occasionally been described in the lung, but little is known about the etiology, morphologic features, histogenesis. and natural history of ixed tumors

these rare pulmonary neoplasms.’

This brief report

describes a malignant mixed tumor of the lung that we recently studied. From the Unit of Pathology, National University of Mexico School of Medicine and the General Hospital, S.S.A., Mexico City, Mexico. “Resident in Pathology, Pathology Unit, National University of Mexico School of Medicine and the General Hospital, S.S.A. tChairman, Pathology Unit, National University of Mexico School of Medicine and the General Hospital, S.S.A.

CHEST,VOL. 58, NO. 1, JULY 1970

MALIGNANTMIXEDTUMOROF LUNG

85 tion of the right main bronchus and bronchial biopsy from this site showed a poorly differentiated epidermoid carcinonla. Additional chest roentgenogra,ns were performed after drainage of the pleural fluid and injection of quinacnne (Atabrine) into the right pleural cavity. A “large mass with calcified areas” was seen within the right middle and lower lobes (Fig I), and a bronchograrn demonstrated extreme sten,sis of the right middle bronchus. Because of rapid deterioration in the patient’s condition no therapy was instituted, and he died shortly after his admis-

sionAt autopsy, the right parietal and visceral pleurae were fused, thickened and invaded by firm, pearly-white tissue continuous with the third and fourth ribs, intercostal muscles and vertebrae. The right lung weighed 850 gin, and the left, 450 gin. The fonner was of finn consistency and presented a large nodular tumor mass in the middle lobe. On cut surfaces, this pale-white tumor was 16 cm in diameter and had well-defined borders. Scattered throughout were calcified and noncalcified cartilaginous nodules and areas of necrosis (Fig 2). The neoplasm appeared to arise from the right middle bronchus, and, due to itS large size, compressed the bronchus and vascular pedide of the right inferior lobe, producing

atelectasis.

Other

findings

of interest

included

invasion of the lower portion o1 the right sipper lobe, the visceral and parietal pleurae, and metastasex to the left fifth rib, thyroid, liver, pancreas, adrenals, kidneys, as well as the medjaxtinal, peripancreatic and right inguinal lyniph nodes. Microscopically, the primary neoplasm was composed of a mixture of epithelial and mesenchymal tissues, though only FIGuRE 1. Lateral view of chest roentgenogram showing in the middle and lower lobes a large rounded mass with irregular cakific deposits. CASE REPORT This 87-year-old man was admitted to the hospital with a past history of heavy cigarette smoking of 46 years’ duration. Six months before adniission he had sustained a contusion on the anterior ‘all of the right hemnithorax. His present illness began 13 months before his death, with a productive cough yielding a moderate amount of nisty-colored sputum which on occasion was blood streaked dr frankly bloody. Three months before death, he developed an intense, stabbing pain in the right anterior chest wall, irregular fever that ranged from 37#{176}C to 38.5#{176}C, and mild dyspnea. On physical examination the most or.tstanding findings were an area of dullness and diminished breath sounds about the base of the right hemithorax and slight enlargement of the liver which could not be palpated with accuracy due to generalized abdominal muscular resistance. Chest roentgenograms confinned the presence of a right pleural effusion. Other laboratory examinations were within normal limits, except for a white blood cell count (WBC) of 22,000/mm3, with 79 percent neotrophils and serum albumin of 2.7 gm/TOO ml, with a globulin of 3.2 gm. Several right thoracenteses were performed, and on each occasion 200 to 250 nil of serosanguineous fluid was obtained. The pleural fluid was negative on bacteriologic examination but the cytologic examination was positive for malignant cells. Subsequent cytologic examinations of sputum and bronchial washings were also positive for malignant cells, consistent with undifferentiated small cell type of carcinoma of the lung. Bilateral scalene node biopsy was perfonned, and rnetastatic adenocarcinoma was found in one of the left scalene lymph nodes. Bronchoscopy revealed tumor infiltra-

CHEST, VOL. 58, NO. 1, JULY 1970

lIGUnE 2. A large nodular tumor with well-defined borders replaces the middle lobe. Note calcified and noncalcified cartilaginous nodules, invasion of pleurae amid collapse of

losver lobe.

VAOlLLO-BRICEO, FEDER AND ALBORES-SAAVEDRA

86 the former exhibited

cytologic characteristics

of malignancy.

Small round or spindle-shaped cells identical to those of small cell undifferentiated carcinoma of the lung formed the greatest portion of the neoplasm. However, in scattered foci, the cells were columnar and formed glandular structures of s’ariuble size and shape; occasionally mucus secreting cells and foci of squamous cell carcinoma vere also identified ( Fig 6). The predominant niesenchyniat Component va.s mature

hyaline cartilage while mvxoid and adipose tissues were less conspicuous. The Illixture of small cell undifferentiated carcinonm and rounded masses of mature hyaline cartilage produced a striking and unique tissue cc,mbination (Fig 3). Here and there, many of the various cellular elements of the neoplasm were admixed; ie, small cell undifferentiated carcinonla, aclenocarcinoma, hyaline cartilage, mnyxoid tissue and adipose tj5so (Fig 4, 5). The hyaline cartilage was also growing in an irregular fashion along the walls of the pulnhmnary vessels and bronchioles. Extensive areas of necrosis and focal calcification of hyalifle cartilage were also observed. Except for some of the lymph nodes which contained aclenocarcinorna, all the metastatic deposits were composed exclusivelyoi small cell undifferentiated carcinoma. The case was shown to Dr. Averill Liebow, of the University of California at San Diego, who agreed with the diagnosis of malignant mixed tumor of the lung.

DiscussioN This is an exceedingly rare tumor. Only one malignant mixed tumor of embryonal type was observed and illustrated in the series of 5,000 malignant tumors of the lung at the Memorial Hospital in New York. No such cases were foimd in the 3,965 bronchogenic carcinomas reported by Henderson and Curwen. The same was true for the 1,000 cases of Moersch and McDonald5 and for the 666 lung carcinomas

of Ashley and Davies.6

In our small series of 167 autopsies of bronchogenic

carcinoma,

this

example of malignant that we have observed.

case represents the first mixed tumor of the lung

Our case falls into the Group IX, subtype I, of the

Vorld Health Organization histopathologic types of lung tumors,’ and in some ways, it is similar to that

Fmc.caE4. Hyaline cartilage ,nyxoid and adipose tissue intermingled with small cell undifferentiated carcinoma and adenocarcinoma. described by Flanagan and co-workers.7 This latter neoplasm, however, differs from ours in that its

predominant epithelial component was epidermoid carcinoma and that in addition to cartilage it had bone and osteoid which were interpreted as metaplasia of the stroma. This interpretation was made on pure histologic grounds; therefore it has the

limitations of such a method. Due to the absence of skin, hair, sebaceous

hand, the lack of malignant

features

of the mesen-

chymal components of the mixed tumor make the term carcinosarcoma unwarranted. However, carcinosarcomas with or without bone and cartilage formation, do occur primarily in the lung and are now considered a definite clinicopathologic entity.9-’ 2 The most important morphologic features of this

mixed tumor can be summarized as follows: 1) it was a large nodular

neoplasm,

with well-defined

borders and partially calcilled cartilaginous nodules distributed at random; 2) three distinct types of epithelial carcinomatous components were present (small cell undifferentiated carcinoma, adenocarcinoma and epidermoid carcinoma), of which the small cell undifferentiated component was the most abundant in both the primary neoplasm and the metastases; and 3) the mature mesenchymal tissues (hyaline cartilage, myeloid and adipose tissues) lacked cytologic characteristics of malignancy and did not metastasize. The histogenesis

FmcunE3. Photomicrograph of the primary tumor depicting a mixture of small cell undifferentiated carcinoma and masses of mature hyaline cartilage.

glands

and pancreas in mixed tumors of the lung, they can easily be distinguished from pulmonary teratomas which usually contain these tissues.S On the other

of this tumor

has not been

satisfactorily clarified. Two main hypotheses could be advanced to explain the mesenchymal components: 1) they represent metaplasia of the stroma induced by the epithelial elements, or 2) they originate from the epithelial tissues. If the former

CHEST,VOL. 58, NO. 1, JULY 1970

MALIGNANT MIXED TUMOR OF LUNG

87 malignant mixed tumor of the lung is better than that of other bronchogenic carcinomas; however, in the present case the clinical behavior of the neoplasm was similar to that of the small cell undifferentiated carcinoma. The only distinctive clinical feature was the presence of irregular calcific deposits within the tumor mass which were

visualized

‘‘: FIGuRE 5. Cartilage growmg along the wall of a pulmonary vessel. Balance of microscopic findings similar to Figure 4.

hypothesis is correct, the term bronchogenic carcinoma with myxoid fatty and cartilaginous metaplasia would be a better name for this tumor, as indicated by Flanagan and co-workers. As vet, there is no unequivocal evidence in favor of either of the hypotheses.

It is diThcult to believe that the

neoplastic epitheliuni

could be transformed

into

adult adipose tissue. Histochemical and electromicroscopic studies may throw some light onto this problem. If the teratomas are excluded, a small number of tumors from other organs characterized by a mix-

ture of epithelial and mesenchvmal tissues (mainly cartilage and bone) remain. The best known are mixed tumors of salivary glands,’ breast carcinoma,14 mixed tumors of the uterus,1 transitional cell carcinoma of bladder,’” adenocarcinonia of colon,’ and follicular carcinoma of thyroid.’8 In most of these neoplasms, as in pulmonary mixed tumors, the mechanism of bone and cartilage formation is controversial. It has been suggested that the prognosis of the

by chest roentgenograms.

Since cal-

cifications seldom occur iii bronchogenic carcinoma they are considered to be an important diagnostic feature, Finally, it is of interest to point out that had autopsy not been done, the neoplasm would have been diagnosed as a mixed or combined bronchogenie carcinoma (small cell undifferentiated, epidermoid and adenocarcinoma) because the mesenchymal elements were not present in the biopsy specimens. A small biopsy specimen of the primary neoplasm or a large fragment of tissue from a metastasis might easily miss the mesenchymal components due to their focal distribution within the primary lesion and their absence in the metastases. This may be one of the factors that could explain the extreme rarity of this neoplasm. REFEBENCES

1 World Health Organization: Histological typing of lung tumors, WHO, Geneva, Switzerland, 1967 2 Liebow, AA: Tumors of the lower respiratory tract, Atlas of Tumor Pathology. see V. fase. 17, Armed Forces Institute of Pathology, Washington, DC, 1952 3 Watson, WL: A study of five thousand Memorial Hospital cases, in Lung Cancer, St. Louis, The C. V. Mosby Co., 1968 4 Henderson, Xl, Curwen, MY: Cancer of the lung in South West England and London: An epidemiological study of histopathological type, Brit J Cancer, 15:19, 1961 5 Moersch, HJ. McDonald, JF: The significance of cell types in bronchogenic carcinomas, Dis Chest 23:621, 1953 6 Ashley, DJB, Davies, DH: Cancer of the lung, histology and biological behavior. Cancer 20:165, 1967 7 Flanagan, P, McCraken, AW, Cross, RM: Squamous carcinoma of the lung with osteocartilaginous stroma, I Clin Path 18:403, 1965 8 Collier, FC, Dowling, EA, Plott, D, et al: Teratoma of the lung, Arch Path, 68:138, 1959 9 Rergmann, Xl, Ackerman, LV, Kemler, RL: Careinosarcoma of the lung, Cancer 4:919, 1951 10 Drury, BAR, Stirland, RNI: Carcinosarcomatous tumors of the respiratory tract,J Path Bact77:543, 1959 ii Jenkins, BJ: Carcinosarcoma of the lung, report of a case and review of the literature, J Thorac Cardiovasc Surg 55:657, 1968

FIGURE6. Small focus of squamous cell carcinoma lying in an abundant fibrous stroma which also contains groups of small undifferentiated

carcinoma cells.

CHEST, VOL. 58, NO. 1, JULY 1970

12 Stackhouse, EM, Harrison, EC, Jr, Ellis, FH, Jr: Primary mixed malignancies of lung: carcinosarcoma and biastoma, J Thorac Cardiovasc Surg 57:3S5, 1969 13 Welsh, BA. Meyer, AT: Mixed tsm,ors of hsman salivary gland, Arch Path 85:433, 1968 14 McDivitt, RW, Stewart, FW, Berg, JW: Thmors of the

VADILLO-BRICENO,FEDER AND ALBORES-SAAVEDRA

88

breast, in Atlas of Tumor Pathology, second series, fasc. 2, Armed Forces Institute of Pathology, Washington, D.C. 1968

15 Norris, HJ, Roth, E, Taylor, HB: \Iesenchymal tumors of the uterus, Obstet Cynec 28:57, 1966 16 Pang, LSC: Bony and cartilaginous tumors of the urinary bladder, J Path Bact 76:3,57, 1988

17 Engel, S. Dockerty, MB: Calcification and ossification in rectal malignant processes, JAMA 179:347, 1962 18 Albores-Saas’edra, J: Unpublished observations

Reprint requests: Dr. Jorge Albores-Saavedra, Unidad de Patologia Facultad de Medicina, UNAM y Hospital General, S.S.A. Mexico 7, D.F.

Exhilaration Isn’t Always Fun To those who are fascinated by oddities of ancient history, early beginnings of human culture, mystifying fragments of archeology and awe-inspiring, spectacular beauty of Nature, the majestic sight of Cuzco, Machu Piechu and their environs makes it worth going to South America. Cuzco, the City of Legendary Splendor, the City of the Sun, Capital and Sacred City of the Incas is two hours by air from Lima, Peru. It lies in a funnelshaped valley of the Andes Mountains at an altitude of 11,444 feet. The massive array of ruins of great temples, large palaces and assortment of other structures offer an unforgettable sight. There are the relics of a magnificent Inca bath, an exquisite fountain, an enormous amphi(heater and other surprising attractions. Nearby stands a fortress protected by a 1200 foot wall. The latter svas built of giant-sized blocks of granite. One of its boulders is 38 feet long, 18 feet high and 12 feet thick. Even stones used for the construction of buildings, hewed out of the surrounding mountains, weigh several tons. These huge units were moved to location without the use of wheels, undiscovered by the Incas, and fitted together with inimitable precision, without the aid of pulleys or mortar. Their astonishing structural strength is attested by the fact that they have svithstood the devastating ravages of severe earthquakes. The secret of this amazing perfection of Inca craftsmanship still has not been solved by modern engineering science. In the outskirts, terraced, cultivated mountainsides, orchards and gardens exhibit a prodigious mixture of sumptuous colors. Machu Picehu is only 75 miles from Cuzco, situated in a valley at an altitude of slightly over 6,000 feet. Ruins of this ancient citadel of the Inca empire represent a truly thrilling apocalypse. The puritanical simplicity and silent dignity of widespread megalithic ruins awaken visions of striving culture of ancient days. Attractive as these sights may be, it is well to keep in mind that arriving by plane from Lima, Peru, only 500 feet above sea level, to Cuzco (11,444 feet) is literally a breath-taking experience. Physiologic and pulmonary function studies re.

veal interesting findings in individuals after abrupt transportation from near sea level to high altitudes. There is lowering of arterial oxygen tension and decrease in arterial Pco. (respiratory alkalosis with increased pH of the blood) - The vital capacity of the lung is decreased and its residual volume is increased. Initially, hyperventila. tion is brought about by hypoxia through the aortic and carotid chemoreceptors. As the result of hyperventila. tion there is some increase in oxygen consumption. In susceptible persons, particularly under the influence of physical or emotional strain, after a heavy meal or on exposure to cold, evidence of pulmonary edema may be noted on physical and x-ray examination. Due to peripheral vasoconstriction, the central venous pressure is in. creased. There is pulmonary hypertension. According to authoritative views, the latter as well as pulmonary edema are brought about by postcapillary venoconstriction. Also, electrocardiographic evidence of right ventricular overloading has been recorded on the first day in subjects ascending to high altitudes, even without demonstrable pulmonary edema. Simultaneously, disturbing or very serious symptoms may develop in subjects follosving sudden ascent to high attitude. These include headache, restlessness, vertigo, undue fatigue, muscular weakness and/or inadequate coordination, drowsiness, chest pain, precordial discomfort, palpitation, nausea, vomiting, dyspnea, taehypnea, cyanosis, cough, interference with mentation, disorientation. Some of the pertinent comments of Cherniak and Cherniak (Respiration in Health and Disease. Saunders, Philadelphia, 1961) are worth quoting. “When a person becomes acutely hypoxic, he may exhibit either somnolence or lassitude Or a sense of comfort, well-being and self-satisfaction, which is often associated with outbursts of hilarity or obstreperousness. Judgmen may become impaired to such an extent that the entire clinical picture resembles one of drunkenness.” Andrew

L. Ban yal,

M.D.

CHEST,VOL. 58, NO. 1, JULY 1970