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Primary fibrosarcoma of the lung in a young child
P R I M A R Y F I B R O S A R C O M A OF T H E L U N G I N A Y O U N G C H I L D A CASE TREATED BY LOBECTO~Iu AND COBALT T H E R A P Y F.
S.
(~ERBASI, ~ [ . D . ,
A.
M.D., COMMANDER ( M C ) , R. S. KmLER, M.D.
M . MARGILETH,
USN, AND
DETROIT, M I C H .
IMARY fibrosarcoma of the p Rlung, in general, is a relatively
on the following d a y became black a n d blue. F i v e d a y s p r i o r to admisrare condition. The occurrence of sion the p a t i e n t developed a t e m p e r a t u r e of 104 ~ F. rectally. The f e v e r such a lesion in a child u n d e r 3 years o c c u r r e d at the same time t h a t the of age is still more unusual. Review black a n d blue blotches were noted. of the literature revealed one possible The p a t i e n t was seen at F o r t Mccase b y Rosenblum and Gasul2 They A r t h u r , San Pedro, Calif., and given terramycin. The f e v e r subsided in r e p o r t e d a case of p r i m a r y sarcoma two days. The p a t i e n t seemed to be of the lung in a 29-month-old child. restless at night and his appetite W h e t h e r this was a fibrosarcoma or was poor. Three d a y s p r i o r to adsome other t y p e of lesion was not mission the p a r e n t s noted t h a t the child seemed to be h a v i n g some diffistated. culty breathing. He had also comBecause of the e x t r e m e r a r i t y of plained of pain in both feet. He was this condition and the lack of re- seen at F o r t M c A r t h u r and because sponse to e a r l y l o b e c t o m y and cobalt of the history of dyspnea, an x - r a y of the chest was taken. The x~ray is 60 t h e r a p y , we are p r o m p t e d to resaid to have revealed a "cannon ball" p o r t this case. lesion in the r i g h t chest. The p a t i e n t was r e f e r r e d to the Corona N a v a l CASE REPORT H o s p i t a l f o r t r e a t m e n t of the pulmon a r y lesion. l~. T., case 41086, a 2-year-9-1nonthF a m i l y history and d e v e l o p m e n t a l old white boy, was first seen at the h i s t o r y were normal. U.S. N a v a l Hdspital, Corona, Calif., The physical e x a m i n a t i o n revealed on Feb. 27, 1956. The history rea well-developed, well-nourished child vealed t h a t ten d a y s p r i o r to admission the child had a skin lesion on who a p p e a r e d to be about 3 y e a r s of age. H e was not in acute distress the ankles a n d feet which a p p e a r e d but did h a v e a minimal e x p i r a t o r y to be due to insect bites. The patient grunt. H e was 37 inches tall. W e i g h t was t r e a t e d by his local physician T e m p e r a t u r e was with v i t a m i n K, v i t a m i n C, and elixir was 35 pounds. 102.2 ~ F. rectally. Blood pressure of Benadryl. In spite of the treatwas 100/40. Physical examination m e n t the rash s p r e a d u p the legs. was e n t i r e l y n o r m a l except for the The rash was present on the b u t t o c k s T h e r e was minimal ecthe n e x t d a y and the lesion was de- following: chymoses os the left u p p e r eyelid. scribed as "large, red welts" which Small, s h o t t y l y m p h nodes were noted F r o m the 1)epartment of Surgery, Alexin both axilla. These were nontender. a n d e r Blain Hospital, Detroit, Mich. ; U. S. N a v a l Hospital, Chelsea, Mass. ; a n d DepartThe skin on the legs, buttocks, and merit of Radiology, Carobil Hospital, Nora r m s showed numerous petechiae and walk, CaliL 488
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fresh and old p u r p u r i c spots. There was a swelling and tenderness of the right testicle and spermatic cord, and eechylnoses o[ the overlying scrotal tissue. L a b o r a t o r y findings were as follows: Three complete blood counts were n o r m a l as well as plateiet counts which r a n g e d f~'om 352,000 to 374,000. The bleeding time was 2 m i n u t e s and
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sity in the lower half of the r i g h t lung field which measured a p p r o x i m a t e l y 6 era. in diameter. The bol'ders were fairly sharply outlined, and the mass was seen in its ent i r e t y in the r i g h t lower lobe. It was n o t connected to the d i a p h r a g m or to the p o s t e r i o r chest wall. The r i g h t m i n o r fissure and the l o w e r portion of the m a j o r fissure were also
B.
~'ig. 1 . - - A , P r e o p e r a t i v e P o s t e r o a n t e r i o r r o e n t g e n o g r a m of t h e c h e s t i l l u s t r a t i n g a l a r g e m a s s o c c u p y i n g a b o u t o n e - h a l f of t h e r i g h t h e m i t h o r a x . B, L a t e r a l v i e w s h o w i n g t h e t u m o r to o c c u p y t h e r i g h t l o w e r lobe.
the Lee-White coagulation time was normal. A t h r o a t culture showed n o r m a l flora, and a blood culture was negative. A blood u r e a nitrogen on M a r c h 1 was 14.75 rag. p e r cent. Two urine analyses were normal. Bone m a r r o w studies were normal. X - r a y s of the chest t a k e n on Feb. 24 and 29, 1956, showed a welldefined, circular, homogeneous den-
seen as slightly a c c e n t u a t e d lines, and there was no evidence of atelectasis of the middle lobe. There was no evidence of compression of the surr o u n d i n g p u l m o n a r y tissue n o r was there a n y displacement of the cardiac or mediastinal s t r u c t u r e s (Fig. 1). X - r a y s of the skull and long bones and an i n t r a v e n o u s p y e ] o g r a m were normal.
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On March 1, t956, the patient was afebrile and the pur pur a appeared to be more coalescent and seemed to be less extensive. The testicle on the right was definitely swollen, but there was less swelling of the cord. A urological consultant saw the patient and felt that the testicular swellings were most likely due to the purpuric processes. The patient was seen by a thoracic surgeon (F. S. G.), who noted that there were decreased breath sounds and dullness over the right lower lung field both anteriorly and posteriorly. Nontender, bilateral, small cervical nodes were also noted. The liver was found to be one fingerbreadth below the right costal margin, but the spleen was not palpable. It was the opinion of the surgeon that this was a primary neoplasm of the lung or a large fluid-filled cyst. E x p lo r ato r y thoracotomy was recommended after the purpuric rash had cleared. During the next two days the purpura did fade. The swelling in the right testicle also decreased. One week following admission, the purpuric spots had practically disappeared. However, on the following day they recurred. A Rumpel-Leede test at this date was negative. The child was given antibiotics and vitamin K, and two days later the rash had practically disappeared. It was decided that thoracotomy should be performed. On March 9 the patient was taken to the operating room and a right parascapular incision made. The fifth interspace was incised. The pleural space was partially obliterated by rather firm adhesions between the superior dorsal segment of the right lower lobe and the parietal pleura. These adhesions were divided. A large mass was noted occupying more than half of the right lower lobe. This mass was completely confined to the right lower lobe and was of firm consistency. The lymph nodes in the hi]at area were somewhat larger than norreal and had a brownish hue. The pulmonary ar ter y going to the right lower lobe was isolated in the ma-
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jor fissure and the segmental branches ligated and divided. The inferior pulmonary vein was isolated, ligated, and divided. The bronchus to the lower lobe was readily located. The superior dorsal segmental bronchus was isolated and divided and its stump sutured with interrupted 4-0 silk sutures. The lower lobe bronchus distal to the superior dorsal segmental bronchus was then divided and its stump reapproximated with interrupted 4-0 silk sutures. A penicillin and streptomycin solution was placed in the pleural space and a thoracotomy tube connected to water-sealed drainage. The wound was then closed. The pathological report was as follows: "The specimen consists of the right lower lobe of the lung. Occupying the major portion of the structure is a tumor mass 6 cm. in diameter, the cut surface of which bulges. It is, for the most part, fairly soft, uniform gray, and resembles lymphoid tissue. The borders of the tumor are sharply circumscribed and there appears to be a fibrous capsule about it. The surrounding lung is collapsed. There is no invasion of the bronchi or veins. Portions of the tumor are hemorrhagic and necrotic. A small bronchial lymph node 8 mm. in diameter is not invaded by tumor. The microscopic sections revealed the tumor to be composed of solid masses of cells resembling embryonic mesenchyme. In some areas these cells are stellate and widely spaced, while in others they are condensed into sheets and nodular masses of closely packed spindle cells seen to project into the lumen of these vascular spaces and in many instances there appears to be no endothelium separating the lumen from the tumor cells. Mitoses are quite frequent. In the sections examined, there is no differentiation of these cells toward muscle, cartilage or epithelium. Frequently there are vacuolated ~ells containing lipoid droplets. The surrounding lung is compressed apparently by expansion of the tumor,
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there is a zone of reactive fibrosis forming a capsule about the tumor. Toward the hilum the capsule is penetrated microscopically by masses of tumor cells. Two bronchial lymph nodes present in the sections are not involved by tumor. The final diagnosis was undifferentiated mesenchymal sarcoma, which suggested its designation as an anaplastic fibrosarcoma" (Fig. 2).
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more soundly and was breathing with no difficulty. He was able to elevate both arms above his head without any distress. There was no cough. Examination of the patient at this time revealed only a slight decrease of breath sounds over the right lower chest. Several small areas of petechiae were noted on the flexure surface of the left knee and also on the scrotum.
B.
l~ig. 2 . - - A a n d B, P h o t o m i c r o g r a p h s of t h e f i b r o s a r e o m s ~ o f t h e l u n g . A, d e m o n s t r a t e s t h e s p i n d l e - s h a p e d cells c l o s e l y p m c k e d i n s h e e t s a n d h a v i n g a m e s e n c h y m a l a p p e a r a n c e ( X 4 0 0 ) . B, i l l u s t r a t e s , u n d e r h i g h e r P o w e r , t h a t t h e c e l l s a r e p l e o m o r p h i e a n d a n a p l a s t i c w i t h l i t t l e cytoplasm (X1,060 ; reduction ~).
These slides as well as a portion of the tumor mass were sent to the Armed Forces Institute of Pathology, which concurred in this opinion. The patient's postoperative course was uneventful. On the second postoperative day it was noted that his purpuric rash had practically disappeared. On the sixth postoperative day the patient was discharged from the hospital in very good condition. Five days after leaving the hospital the patient was seen in the outpatient clinic. The patient's parents said that the boy had been sleeping much
On March 26, eleven days after discharge from the hospital, the child had no complaints. He weighed 36 pounds. He was very active about the house and had a good appetite. Physical examination was essentially negative. Laboratory studies on this date showed a blood urea nitrogen of 20.25 mg. per cent, total protein 6.85 rag. per cent, albumin 5.1 Gin. per cent, and globulin 1.75 Gin. per cent. A complete blood count, sedimentation rate, hematocrit, and urinalysis were done and these were all normal. An adequate platelet count was again noted in the blood smear.
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On April 9 the patient seemed to be tiring a little more easily. However, physical examination was entirely normal. X-rays of skull, long bones, and chest were t a k e n and these were i n t e r p r e t e d as normal. On August 7, 1956, the patient was seen in the outpatient d e p a r t m e n t where the parents stated t h a t the boy had developed a cough which had not subsided with t e r r a m y c i n which had been given b y his local physician. X-rays of the chest were t a k e n at that time and it was noted that there was a large hilar node and a questionable infiltrate in the right u p p e r lobe parenchyma. The child had not lost weight and had developed no dyspnea. He did not complain of any chest pain. The patient was a d m i t t e d to the L e t t e r m a n A r m y Hospital (case 4243050) on A u g u s t 14, 1956. The ternp e r a t u r e was 100.4 ~ F. W e i g h t was 37 pounds. Blood pressure was 108/ 62. He was f o u n d to be a welldeveloped, well-nourished blond child in no distress. A firm ~/2 b y 1/~ cm. node was palpated in each supraclavicular area. Chest expansion was equal, and the lungs were clear and resonant with no r~les audible. There were no nodular masses along the incision. The rest of the physical examination was essentially normal. L a b o r a t o r y findings at this time revealed a white blood count to be 3,600, neutrophils 29, lymphocytes 48, monocytes 15, eosinophils 5, and basephils 3. Hemoglobin was 12.5 Gin. Bleeding and coagulation times were normal. H e m a t o c r i t was 38 per cent. Repeat white blood cell counts varied from 5,000 to 10,000, and the differentim counts also showed considerable variation. Urine analysis was negarive. On Aug. 28, 1956, a r i g h t supraclavicular node biopsy was performed. No t u m o r cells were found in these nodes. Cultures from these nodes were also negative. On September 11 a bone survey, including skull and chest x-rays, was normal except for a minimal soft tissue den-
OF P E D I A T R I C S
sity in the right lower posterior lung field. On September 13 a right thoracotomy was performed. T u m o r tissue was f o u n d in the parietal pleura along the line of the previous incision. The hilum was infiltrated with t u m o r tissue, most of which appeared to be encapsulated b y a thin, bluishwhite membrane. It was realized that there was massive involvement of the mediastinum and that nothing surgical could be done which would be of benefit to the child. Therefore, the chest was closed a f t e r a thoracot~ omy tube had been placed. The child recovered and was discharged from the hospital one week a f t e r the operation. He was r e f e r r e d to a n o t h e r hospital f o r radiation therapy. He was given cobalt 60 at a distance of 75 em. t h r o u g h 4 portals. T h e r a p y was begun on September 27 and completed on November 29. Each field was t r e a t e d to completion and then the n e x t was started. Thus, p o r t a l 1 (AP mediastinum) was treated daily up to 3,900 r. (skin), then 2 (right PA 45 degrees) was started and 680 r. given. Following this, 3 (right P A chest) and 4 (right A P chest) were instituted and 3,000 r. and 3,200 r., respectively, administered. Approximately 200 r. skin dose was given at each t r e a t m e n t which was daily, except S a t u r d a y and Sunday. The total t u m o r doses were 3,247 r. to the mediastinum and 4,462 r. to the right lung. The fields were stationary, and measured as follows: portal 1 was 6 b y 15 cm., p o r t a l 2, 2 by 15 cm., portal 3, 10 by 13 cm., and portal 4, 10 b y 12 cm. On Jan. 10, 1957, he received a skin dose of 100 r. and a t u m o r dose of 75 r. to the A P right chest t h r o u g h a field of 12 by 15 cm. The following day a skin dose of 50 r. and a t u m o r dose of 38 r. to the A P left chest t h r o u g h a field of 8 by 15 cm. was given. This t h e r a p y did produce a slight decrease in the size of the metastatic nodules.
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On J a n u a r y 6 the boy was readmitted to the hospital because of lethargy, anorexia, and cough. Following x-rays, he was f o u n d to have a massive pleural effusion oll the right lung and numerous spherical nodules in the left lung. L a b o r a t o r y examination at this time revealed a normal urine analysis and a hemoglobin of 10.5 Gin. The white blood count was 12,150 with 88 per cent neutrophils and 8 per cent lymphocytes. He was treated
Fig. 3.--Posteroanterior roentgenogram and one month before death. The right erous metastatic nodules throughout the
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absent breath sounds. Harsh breath sounds were audible over the left lung. L a b o r a t o r y d a t a at this time revealed a hemoglobin of 10.5 Gin. The white blood count was 2,800, with 66 per cent p o l y m o r p h o n u c l e a r cells, 30 per cent ]ymphocytes, 3 per cent monoeytes, and 1 per cent eosinophils. A r o e n t g e n o g r a m of the chest revealed the r i g h t side to be completely ()pacified, a finding consistent With the ~)resenee of large amounts of fluid (Fig. 3). The metastatic nod-
of the chest approximately one )'ear after surgery hemithorax is completely opaeifled. There are numleft lung.
with radiation, terramycin, thoraeentesis, plus Meticorten and imp r o v e d enough to r e t u r n home on J a n u a r y 18. However, he still remained somewhat lethargic and had his chronic cough. His final admission to the hospital was on F e b r u a r y 8 because of dyspnea. Physical examination revealed an acutely ill boy in m a r k e d respiratory distress. Respirations were 100 per minute. He had a harsh cough productive of a small a m o u n t of pinkish sputum. There was only slight movement of the right thoracic cage. The entire right chest was dull with
ules appeared to have increased slightly in size on the le~t side. Thoracentesis was a t t e m p t e d the day a f t e r admission, but no fluid was obtained. Then it was felt t h a t this opacity seen on the x-ray was consolidated lung probably replaced by tumor tissue and not fluid. He was treated with antibiotics and morphia as indicated. Ile died on March 10, ]957. Autopsy showed an extensive t u m o r in the right hing and pleural cavity with extension of the tumor to the d i a p h r a g m and to the liver. There were multiple metastatic nodules in
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the left l u n g - b u t none elsewhere. There was atelectasis of the left lower lobe. Mild chronic passive congestion of the lungs and liver was noted. An emphysematous bleb was noted in the left lower lobe. The microscopic examination of the tumor tissue from the autopsy specimens were the same as that seen in the previous sections of the tumor removed surgically, that is, anaplastic fibrosarcoma of the lung. DISCUSSION
It is difficult to determine the incidence of fibrosarcoma of the lung since little attempt has been made, until the past ten years, to classify these tumors other than as bronchogenie sarcoma of the lung. Furthermore, the number o~ fibrosarcomas reported are too few to be of any statistical significance. Stout, 2 in 1948, emphasized that the use of terms such as "neurogenic sarcoma" and "spindle cell sarcoma" were meaningless, that they were causing a great deal of confusion, and that they should be abandoned. Since then, more specific classifications of sarcomas of the lung have been made and have thus helped to clarify the literature on this subject2 P r i m a r y bronchopulmonary fibrosarcoma occurs at all ages. Few cases have been reported in older children, but we have been unable to find any case, other than our own, under 3 years of age. 4-6 These may arise in the larger bronchi or in the lung parenchyma. In our case the tumor arose in the lung parenchyma. Jensik 7 had a 5-year-old patient with an intraluminal bronchial fibrosarcoma at the orifice of the right middle lobe. He performed a right middle and lower lobectomy. The child is well
OF P E D I A T R I C S
one year postoperatively. Curry and Fuchs 8 reported a case in which the child expectorated a fibrosarcoma of the bronchus and was well with no sign of recurrence four years later. Our patient was not as fortunate. It is infrequent that one can make an exact cytological diagnosis of such a tumor before surgery. Occasionally bronchial secretions, bronchial, a n d / or lymph node biopsy have revealed the exact nature of the lesion. Some of the conditions which were considered in the differential diagnosis included hamartoma, postinflammatory "tumor," bronchogenic cyst, fibroma, carcinoma, and other types of sarcoma such as leiomyosarcoma, granuloma, and teratoma. We were unable to make a definite cytological diagnosis preoperatively in this case. We are unable to assess the value of surgical excision a n d / o r x-ray therapy in this condition from the study of the few cases that have been reported in the literature. The welldifferentiated fibrosarcomas appear to have a better prognosis, as would be expected, than the undifferentiated anaplastic type. We feel that surgical excision is mandatory for a number of reasons: (1) Frequently, it is necessary in order to make a definite diagnosis. (2) It offers palliative t herapy if nothing else, that is, the dyspnea, cough, hemoptysis, etc., that these patients frequently have are relieved temporarily. (The dyspnea did disappear in our case.) (3) It is the only form of therapy available t hat offers any hope of cure. Ochsner and his co-workers 9 recently reported a patient with leiomyosarcoma of the lung which he removed in 1936, and the patient is still alive and well. In our case, cobalt therapy
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was i n s t i t u t e d e m p i r i c a l l y , f o r we d i d n o t k n o w w h e t h e r t h i s t y p e o{ t r e a t m e n t w o u l d be o f a n y b e n e f i t o r not. W e r e a l i z e d t h a t , in g e n e r a l , fibrosarcomas are relatively radioresistant to r a d i a t i o n t h e r a p y , b u t w e h o p e d t h a t t h i s case m i g h t p r o v e t o be t h e exception. T h e r e w a s a s l i g h t dec r e a s e i n t h e size of t h e m e t a s t a t i c n o d u l e s f o l l o w i n g t h e i r i r r a d i a t i o n , as n o t e d b y a r o e n t g e n film of t h e chest, but this was hardly worth mentioning. N o s u b j e c t i v e i m p r o v e m e n t occurred. As noted, the patient died t h i r t e e n m o n t h s a f t e r t h e o n s e t of t h e symptoms despite the methods of therapy instituted. SUMMARY
P r i m a r y f i b r o s a r c o m a of t h e l u n g in a 2-year-9-month-old child has b e e n r e p o r t e d . T h i s is t h e y o u n g e s t case o f t h i s t y p e of s a r c o m a o f t h e lung ever recorded, and the only case recorded in a child treated by lobectomy and cobalt therapy. This was a very anaplastic fibrosarcoma w h i c h r e s p o n d e d p o o r l y to t h e a b o v e mentioned therapy. Excision of the
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lesion relieved the boy's dyspnea temporarily, and the cobalt therapy had l i t t l e o r no t h e r a p e u t i c v a l u e . The patient developed extensive metastases a n d d i e d t h i r t e e n m o n t h s a f t e r t h e m~set of s y m p t o m s . We wish to gratefully acknowledge the cooperation of the Armed Forces Institute of Pathology for making available the photomicrographs of the tumor and their assistance in interpreting the nature of the tumor. REFERENCES
1. Rosenblum, P., and Gasul, B.: A Case of Primary Sarcoma of the Lung in an Infant Twenty-Nine Months of Age, Arch. Pediat. 48: 63, 1931. 2. Stout, A. P.: Fibrosarcoma, Cancer 1: 30, 1948. 3. Hochberg, L. A., and Crastnopo], P.: Primary Sarcoma of the Bronchus and Lung, Arch. Surg. 73: 74, 1956. 4. Black, H.: Fibrosarcoma of the Bronchus, J. Thoracic Surg. 19: 123, 1950. 5. Lewis, L: Sarcoma of the Bronchus~ Proc. Roy. Soc. Med. 40: 119, 1947. 6. ])rewes, J., and Willmann, K. H.: Das primi~re Lungensarkom, Arch. klin. Chir. 274: 95, 1953. 7. Jensik, R. J.: Personal Communication. 8. Curry, J. J., and Fuchs, J. E.: Expectoration of a Fibrosarcoma, J. Thoracic Surg. 19: 135, 1950. 9. Ochsner, S., and Ochsner, A.: Primary Sarcoma of the Lung, Ochsner Clini'c Reports 3: 105, 1957.
S.
(~ERBASI, ~ [ . D . ,
A.
M.D., COMMANDER ( M C ) , R. S. KmLER, M.D.
M . MARGILETH,
USN, AND
DETROIT, M I C H .
IMARY fibrosarcoma of the p Rlung, in general, is a relatively
on the following d a y became black a n d blue. F i v e d a y s p r i o r to admisrare condition. The occurrence of sion the p a t i e n t developed a t e m p e r a t u r e of 104 ~ F. rectally. The f e v e r such a lesion in a child u n d e r 3 years o c c u r r e d at the same time t h a t the of age is still more unusual. Review black a n d blue blotches were noted. of the literature revealed one possible The p a t i e n t was seen at F o r t Mccase b y Rosenblum and Gasul2 They A r t h u r , San Pedro, Calif., and given terramycin. The f e v e r subsided in r e p o r t e d a case of p r i m a r y sarcoma two days. The p a t i e n t seemed to be of the lung in a 29-month-old child. restless at night and his appetite W h e t h e r this was a fibrosarcoma or was poor. Three d a y s p r i o r to adsome other t y p e of lesion was not mission the p a r e n t s noted t h a t the child seemed to be h a v i n g some diffistated. culty breathing. He had also comBecause of the e x t r e m e r a r i t y of plained of pain in both feet. He was this condition and the lack of re- seen at F o r t M c A r t h u r and because sponse to e a r l y l o b e c t o m y and cobalt of the history of dyspnea, an x - r a y of the chest was taken. The x~ray is 60 t h e r a p y , we are p r o m p t e d to resaid to have revealed a "cannon ball" p o r t this case. lesion in the r i g h t chest. The p a t i e n t was r e f e r r e d to the Corona N a v a l CASE REPORT H o s p i t a l f o r t r e a t m e n t of the pulmon a r y lesion. l~. T., case 41086, a 2-year-9-1nonthF a m i l y history and d e v e l o p m e n t a l old white boy, was first seen at the h i s t o r y were normal. U.S. N a v a l Hdspital, Corona, Calif., The physical e x a m i n a t i o n revealed on Feb. 27, 1956. The history rea well-developed, well-nourished child vealed t h a t ten d a y s p r i o r to admission the child had a skin lesion on who a p p e a r e d to be about 3 y e a r s of age. H e was not in acute distress the ankles a n d feet which a p p e a r e d but did h a v e a minimal e x p i r a t o r y to be due to insect bites. The patient grunt. H e was 37 inches tall. W e i g h t was t r e a t e d by his local physician T e m p e r a t u r e was with v i t a m i n K, v i t a m i n C, and elixir was 35 pounds. 102.2 ~ F. rectally. Blood pressure of Benadryl. In spite of the treatwas 100/40. Physical examination m e n t the rash s p r e a d u p the legs. was e n t i r e l y n o r m a l except for the The rash was present on the b u t t o c k s T h e r e was minimal ecthe n e x t d a y and the lesion was de- following: chymoses os the left u p p e r eyelid. scribed as "large, red welts" which Small, s h o t t y l y m p h nodes were noted F r o m the 1)epartment of Surgery, Alexin both axilla. These were nontender. a n d e r Blain Hospital, Detroit, Mich. ; U. S. N a v a l Hospital, Chelsea, Mass. ; a n d DepartThe skin on the legs, buttocks, and merit of Radiology, Carobil Hospital, Nora r m s showed numerous petechiae and walk, CaliL 488
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fresh and old p u r p u r i c spots. There was a swelling and tenderness of the right testicle and spermatic cord, and eechylnoses o[ the overlying scrotal tissue. L a b o r a t o r y findings were as follows: Three complete blood counts were n o r m a l as well as plateiet counts which r a n g e d f~'om 352,000 to 374,000. The bleeding time was 2 m i n u t e s and
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sity in the lower half of the r i g h t lung field which measured a p p r o x i m a t e l y 6 era. in diameter. The bol'ders were fairly sharply outlined, and the mass was seen in its ent i r e t y in the r i g h t lower lobe. It was n o t connected to the d i a p h r a g m or to the p o s t e r i o r chest wall. The r i g h t m i n o r fissure and the l o w e r portion of the m a j o r fissure were also
B.
~'ig. 1 . - - A , P r e o p e r a t i v e P o s t e r o a n t e r i o r r o e n t g e n o g r a m of t h e c h e s t i l l u s t r a t i n g a l a r g e m a s s o c c u p y i n g a b o u t o n e - h a l f of t h e r i g h t h e m i t h o r a x . B, L a t e r a l v i e w s h o w i n g t h e t u m o r to o c c u p y t h e r i g h t l o w e r lobe.
the Lee-White coagulation time was normal. A t h r o a t culture showed n o r m a l flora, and a blood culture was negative. A blood u r e a nitrogen on M a r c h 1 was 14.75 rag. p e r cent. Two urine analyses were normal. Bone m a r r o w studies were normal. X - r a y s of the chest t a k e n on Feb. 24 and 29, 1956, showed a welldefined, circular, homogeneous den-
seen as slightly a c c e n t u a t e d lines, and there was no evidence of atelectasis of the middle lobe. There was no evidence of compression of the surr o u n d i n g p u l m o n a r y tissue n o r was there a n y displacement of the cardiac or mediastinal s t r u c t u r e s (Fig. 1). X - r a y s of the skull and long bones and an i n t r a v e n o u s p y e ] o g r a m were normal.
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On March 1, t956, the patient was afebrile and the pur pur a appeared to be more coalescent and seemed to be less extensive. The testicle on the right was definitely swollen, but there was less swelling of the cord. A urological consultant saw the patient and felt that the testicular swellings were most likely due to the purpuric processes. The patient was seen by a thoracic surgeon (F. S. G.), who noted that there were decreased breath sounds and dullness over the right lower lung field both anteriorly and posteriorly. Nontender, bilateral, small cervical nodes were also noted. The liver was found to be one fingerbreadth below the right costal margin, but the spleen was not palpable. It was the opinion of the surgeon that this was a primary neoplasm of the lung or a large fluid-filled cyst. E x p lo r ato r y thoracotomy was recommended after the purpuric rash had cleared. During the next two days the purpura did fade. The swelling in the right testicle also decreased. One week following admission, the purpuric spots had practically disappeared. However, on the following day they recurred. A Rumpel-Leede test at this date was negative. The child was given antibiotics and vitamin K, and two days later the rash had practically disappeared. It was decided that thoracotomy should be performed. On March 9 the patient was taken to the operating room and a right parascapular incision made. The fifth interspace was incised. The pleural space was partially obliterated by rather firm adhesions between the superior dorsal segment of the right lower lobe and the parietal pleura. These adhesions were divided. A large mass was noted occupying more than half of the right lower lobe. This mass was completely confined to the right lower lobe and was of firm consistency. The lymph nodes in the hi]at area were somewhat larger than norreal and had a brownish hue. The pulmonary ar ter y going to the right lower lobe was isolated in the ma-
OF P E D I A T R I C S
jor fissure and the segmental branches ligated and divided. The inferior pulmonary vein was isolated, ligated, and divided. The bronchus to the lower lobe was readily located. The superior dorsal segmental bronchus was isolated and divided and its stump sutured with interrupted 4-0 silk sutures. The lower lobe bronchus distal to the superior dorsal segmental bronchus was then divided and its stump reapproximated with interrupted 4-0 silk sutures. A penicillin and streptomycin solution was placed in the pleural space and a thoracotomy tube connected to water-sealed drainage. The wound was then closed. The pathological report was as follows: "The specimen consists of the right lower lobe of the lung. Occupying the major portion of the structure is a tumor mass 6 cm. in diameter, the cut surface of which bulges. It is, for the most part, fairly soft, uniform gray, and resembles lymphoid tissue. The borders of the tumor are sharply circumscribed and there appears to be a fibrous capsule about it. The surrounding lung is collapsed. There is no invasion of the bronchi or veins. Portions of the tumor are hemorrhagic and necrotic. A small bronchial lymph node 8 mm. in diameter is not invaded by tumor. The microscopic sections revealed the tumor to be composed of solid masses of cells resembling embryonic mesenchyme. In some areas these cells are stellate and widely spaced, while in others they are condensed into sheets and nodular masses of closely packed spindle cells seen to project into the lumen of these vascular spaces and in many instances there appears to be no endothelium separating the lumen from the tumor cells. Mitoses are quite frequent. In the sections examined, there is no differentiation of these cells toward muscle, cartilage or epithelium. Frequently there are vacuolated ~ells containing lipoid droplets. The surrounding lung is compressed apparently by expansion of the tumor,
GERBASI E T A L . :
PRIMARY
there is a zone of reactive fibrosis forming a capsule about the tumor. Toward the hilum the capsule is penetrated microscopically by masses of tumor cells. Two bronchial lymph nodes present in the sections are not involved by tumor. The final diagnosis was undifferentiated mesenchymal sarcoma, which suggested its designation as an anaplastic fibrosarcoma" (Fig. 2).
~-.
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491
more soundly and was breathing with no difficulty. He was able to elevate both arms above his head without any distress. There was no cough. Examination of the patient at this time revealed only a slight decrease of breath sounds over the right lower chest. Several small areas of petechiae were noted on the flexure surface of the left knee and also on the scrotum.
B.
l~ig. 2 . - - A a n d B, P h o t o m i c r o g r a p h s of t h e f i b r o s a r e o m s ~ o f t h e l u n g . A, d e m o n s t r a t e s t h e s p i n d l e - s h a p e d cells c l o s e l y p m c k e d i n s h e e t s a n d h a v i n g a m e s e n c h y m a l a p p e a r a n c e ( X 4 0 0 ) . B, i l l u s t r a t e s , u n d e r h i g h e r P o w e r , t h a t t h e c e l l s a r e p l e o m o r p h i e a n d a n a p l a s t i c w i t h l i t t l e cytoplasm (X1,060 ; reduction ~).
These slides as well as a portion of the tumor mass were sent to the Armed Forces Institute of Pathology, which concurred in this opinion. The patient's postoperative course was uneventful. On the second postoperative day it was noted that his purpuric rash had practically disappeared. On the sixth postoperative day the patient was discharged from the hospital in very good condition. Five days after leaving the hospital the patient was seen in the outpatient clinic. The patient's parents said that the boy had been sleeping much
On March 26, eleven days after discharge from the hospital, the child had no complaints. He weighed 36 pounds. He was very active about the house and had a good appetite. Physical examination was essentially negative. Laboratory studies on this date showed a blood urea nitrogen of 20.25 mg. per cent, total protein 6.85 rag. per cent, albumin 5.1 Gin. per cent, and globulin 1.75 Gin. per cent. A complete blood count, sedimentation rate, hematocrit, and urinalysis were done and these were all normal. An adequate platelet count was again noted in the blood smear.
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On April 9 the patient seemed to be tiring a little more easily. However, physical examination was entirely normal. X-rays of skull, long bones, and chest were t a k e n and these were i n t e r p r e t e d as normal. On August 7, 1956, the patient was seen in the outpatient d e p a r t m e n t where the parents stated t h a t the boy had developed a cough which had not subsided with t e r r a m y c i n which had been given b y his local physician. X-rays of the chest were t a k e n at that time and it was noted that there was a large hilar node and a questionable infiltrate in the right u p p e r lobe parenchyma. The child had not lost weight and had developed no dyspnea. He did not complain of any chest pain. The patient was a d m i t t e d to the L e t t e r m a n A r m y Hospital (case 4243050) on A u g u s t 14, 1956. The ternp e r a t u r e was 100.4 ~ F. W e i g h t was 37 pounds. Blood pressure was 108/ 62. He was f o u n d to be a welldeveloped, well-nourished blond child in no distress. A firm ~/2 b y 1/~ cm. node was palpated in each supraclavicular area. Chest expansion was equal, and the lungs were clear and resonant with no r~les audible. There were no nodular masses along the incision. The rest of the physical examination was essentially normal. L a b o r a t o r y findings at this time revealed a white blood count to be 3,600, neutrophils 29, lymphocytes 48, monocytes 15, eosinophils 5, and basephils 3. Hemoglobin was 12.5 Gin. Bleeding and coagulation times were normal. H e m a t o c r i t was 38 per cent. Repeat white blood cell counts varied from 5,000 to 10,000, and the differentim counts also showed considerable variation. Urine analysis was negarive. On Aug. 28, 1956, a r i g h t supraclavicular node biopsy was performed. No t u m o r cells were found in these nodes. Cultures from these nodes were also negative. On September 11 a bone survey, including skull and chest x-rays, was normal except for a minimal soft tissue den-
OF P E D I A T R I C S
sity in the right lower posterior lung field. On September 13 a right thoracotomy was performed. T u m o r tissue was f o u n d in the parietal pleura along the line of the previous incision. The hilum was infiltrated with t u m o r tissue, most of which appeared to be encapsulated b y a thin, bluishwhite membrane. It was realized that there was massive involvement of the mediastinum and that nothing surgical could be done which would be of benefit to the child. Therefore, the chest was closed a f t e r a thoracot~ omy tube had been placed. The child recovered and was discharged from the hospital one week a f t e r the operation. He was r e f e r r e d to a n o t h e r hospital f o r radiation therapy. He was given cobalt 60 at a distance of 75 em. t h r o u g h 4 portals. T h e r a p y was begun on September 27 and completed on November 29. Each field was t r e a t e d to completion and then the n e x t was started. Thus, p o r t a l 1 (AP mediastinum) was treated daily up to 3,900 r. (skin), then 2 (right PA 45 degrees) was started and 680 r. given. Following this, 3 (right P A chest) and 4 (right A P chest) were instituted and 3,000 r. and 3,200 r., respectively, administered. Approximately 200 r. skin dose was given at each t r e a t m e n t which was daily, except S a t u r d a y and Sunday. The total t u m o r doses were 3,247 r. to the mediastinum and 4,462 r. to the right lung. The fields were stationary, and measured as follows: portal 1 was 6 b y 15 cm., p o r t a l 2, 2 by 15 cm., portal 3, 10 by 13 cm., and portal 4, 10 b y 12 cm. On Jan. 10, 1957, he received a skin dose of 100 r. and a t u m o r dose of 75 r. to the A P right chest t h r o u g h a field of 12 by 15 cm. The following day a skin dose of 50 r. and a t u m o r dose of 38 r. to the A P left chest t h r o u g h a field of 8 by 15 cm. was given. This t h e r a p y did produce a slight decrease in the size of the metastatic nodules.
GERBASI
ET
AL. :
PRIMARY
On J a n u a r y 6 the boy was readmitted to the hospital because of lethargy, anorexia, and cough. Following x-rays, he was f o u n d to have a massive pleural effusion oll the right lung and numerous spherical nodules in the left lung. L a b o r a t o r y examination at this time revealed a normal urine analysis and a hemoglobin of 10.5 Gin. The white blood count was 12,150 with 88 per cent neutrophils and 8 per cent lymphocytes. He was treated
Fig. 3.--Posteroanterior roentgenogram and one month before death. The right erous metastatic nodules throughout the
FIBROSARCOMA
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absent breath sounds. Harsh breath sounds were audible over the left lung. L a b o r a t o r y d a t a at this time revealed a hemoglobin of 10.5 Gin. The white blood count was 2,800, with 66 per cent p o l y m o r p h o n u c l e a r cells, 30 per cent ]ymphocytes, 3 per cent monoeytes, and 1 per cent eosinophils. A r o e n t g e n o g r a m of the chest revealed the r i g h t side to be completely ()pacified, a finding consistent With the ~)resenee of large amounts of fluid (Fig. 3). The metastatic nod-
of the chest approximately one )'ear after surgery hemithorax is completely opaeifled. There are numleft lung.
with radiation, terramycin, thoraeentesis, plus Meticorten and imp r o v e d enough to r e t u r n home on J a n u a r y 18. However, he still remained somewhat lethargic and had his chronic cough. His final admission to the hospital was on F e b r u a r y 8 because of dyspnea. Physical examination revealed an acutely ill boy in m a r k e d respiratory distress. Respirations were 100 per minute. He had a harsh cough productive of a small a m o u n t of pinkish sputum. There was only slight movement of the right thoracic cage. The entire right chest was dull with
ules appeared to have increased slightly in size on the le~t side. Thoracentesis was a t t e m p t e d the day a f t e r admission, but no fluid was obtained. Then it was felt t h a t this opacity seen on the x-ray was consolidated lung probably replaced by tumor tissue and not fluid. He was treated with antibiotics and morphia as indicated. Ile died on March 10, ]957. Autopsy showed an extensive t u m o r in the right hing and pleural cavity with extension of the tumor to the d i a p h r a g m and to the liver. There were multiple metastatic nodules in
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the left l u n g - b u t none elsewhere. There was atelectasis of the left lower lobe. Mild chronic passive congestion of the lungs and liver was noted. An emphysematous bleb was noted in the left lower lobe. The microscopic examination of the tumor tissue from the autopsy specimens were the same as that seen in the previous sections of the tumor removed surgically, that is, anaplastic fibrosarcoma of the lung. DISCUSSION
It is difficult to determine the incidence of fibrosarcoma of the lung since little attempt has been made, until the past ten years, to classify these tumors other than as bronchogenie sarcoma of the lung. Furthermore, the number o~ fibrosarcomas reported are too few to be of any statistical significance. Stout, 2 in 1948, emphasized that the use of terms such as "neurogenic sarcoma" and "spindle cell sarcoma" were meaningless, that they were causing a great deal of confusion, and that they should be abandoned. Since then, more specific classifications of sarcomas of the lung have been made and have thus helped to clarify the literature on this subject2 P r i m a r y bronchopulmonary fibrosarcoma occurs at all ages. Few cases have been reported in older children, but we have been unable to find any case, other than our own, under 3 years of age. 4-6 These may arise in the larger bronchi or in the lung parenchyma. In our case the tumor arose in the lung parenchyma. Jensik 7 had a 5-year-old patient with an intraluminal bronchial fibrosarcoma at the orifice of the right middle lobe. He performed a right middle and lower lobectomy. The child is well
OF P E D I A T R I C S
one year postoperatively. Curry and Fuchs 8 reported a case in which the child expectorated a fibrosarcoma of the bronchus and was well with no sign of recurrence four years later. Our patient was not as fortunate. It is infrequent that one can make an exact cytological diagnosis of such a tumor before surgery. Occasionally bronchial secretions, bronchial, a n d / or lymph node biopsy have revealed the exact nature of the lesion. Some of the conditions which were considered in the differential diagnosis included hamartoma, postinflammatory "tumor," bronchogenic cyst, fibroma, carcinoma, and other types of sarcoma such as leiomyosarcoma, granuloma, and teratoma. We were unable to make a definite cytological diagnosis preoperatively in this case. We are unable to assess the value of surgical excision a n d / o r x-ray therapy in this condition from the study of the few cases that have been reported in the literature. The welldifferentiated fibrosarcomas appear to have a better prognosis, as would be expected, than the undifferentiated anaplastic type. We feel that surgical excision is mandatory for a number of reasons: (1) Frequently, it is necessary in order to make a definite diagnosis. (2) It offers palliative t herapy if nothing else, that is, the dyspnea, cough, hemoptysis, etc., that these patients frequently have are relieved temporarily. (The dyspnea did disappear in our case.) (3) It is the only form of therapy available t hat offers any hope of cure. Ochsner and his co-workers 9 recently reported a patient with leiomyosarcoma of the lung which he removed in 1936, and the patient is still alive and well. In our case, cobalt therapy
GERBASI ET A L . :
PRIMARY
was i n s t i t u t e d e m p i r i c a l l y , f o r we d i d n o t k n o w w h e t h e r t h i s t y p e o{ t r e a t m e n t w o u l d be o f a n y b e n e f i t o r not. W e r e a l i z e d t h a t , in g e n e r a l , fibrosarcomas are relatively radioresistant to r a d i a t i o n t h e r a p y , b u t w e h o p e d t h a t t h i s case m i g h t p r o v e t o be t h e exception. T h e r e w a s a s l i g h t dec r e a s e i n t h e size of t h e m e t a s t a t i c n o d u l e s f o l l o w i n g t h e i r i r r a d i a t i o n , as n o t e d b y a r o e n t g e n film of t h e chest, but this was hardly worth mentioning. N o s u b j e c t i v e i m p r o v e m e n t occurred. As noted, the patient died t h i r t e e n m o n t h s a f t e r t h e o n s e t of t h e symptoms despite the methods of therapy instituted. SUMMARY
P r i m a r y f i b r o s a r c o m a of t h e l u n g in a 2-year-9-month-old child has b e e n r e p o r t e d . T h i s is t h e y o u n g e s t case o f t h i s t y p e of s a r c o m a o f t h e lung ever recorded, and the only case recorded in a child treated by lobectomy and cobalt therapy. This was a very anaplastic fibrosarcoma w h i c h r e s p o n d e d p o o r l y to t h e a b o v e mentioned therapy. Excision of the
F I B R O S A R C O M A OF T H E
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lesion relieved the boy's dyspnea temporarily, and the cobalt therapy had l i t t l e o r no t h e r a p e u t i c v a l u e . The patient developed extensive metastases a n d d i e d t h i r t e e n m o n t h s a f t e r t h e m~set of s y m p t o m s . We wish to gratefully acknowledge the cooperation of the Armed Forces Institute of Pathology for making available the photomicrographs of the tumor and their assistance in interpreting the nature of the tumor. REFERENCES
1. Rosenblum, P., and Gasul, B.: A Case of Primary Sarcoma of the Lung in an Infant Twenty-Nine Months of Age, Arch. Pediat. 48: 63, 1931. 2. Stout, A. P.: Fibrosarcoma, Cancer 1: 30, 1948. 3. Hochberg, L. A., and Crastnopo], P.: Primary Sarcoma of the Bronchus and Lung, Arch. Surg. 73: 74, 1956. 4. Black, H.: Fibrosarcoma of the Bronchus, J. Thoracic Surg. 19: 123, 1950. 5. Lewis, L: Sarcoma of the Bronchus~ Proc. Roy. Soc. Med. 40: 119, 1947. 6. ])rewes, J., and Willmann, K. H.: Das primi~re Lungensarkom, Arch. klin. Chir. 274: 95, 1953. 7. Jensik, R. J.: Personal Communication. 8. Curry, J. J., and Fuchs, J. E.: Expectoration of a Fibrosarcoma, J. Thoracic Surg. 19: 135, 1950. 9. Ochsner, S., and Ochsner, A.: Primary Sarcoma of the Lung, Ochsner Clini'c Reports 3: 105, 1957.