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SOLITARY AMYLOID TUMOR OF THE LUNG
SOLITARY AMYLOID TUMOR OF THE LUNG A Case Report William
L. Craver, M.D., Rochester, N.
Y.
A
tumors are not uncommon in the respiratory tract. Over 100 such cases have been recorded. However, these tumors rarely occur as an iso lated lesion in the pulmonary parenchyma. In 1958, Prowse 1 reviewed 18 cases which included 2 of his own. He divided them clinically into three groups: (1) Tumor-like deposits of amyloid in the lungs (4 cases). All patients were asymptomatic and had multiple nodules which were found incidentally at autopsy after death from an unrelated cause. (2) Amyloid deposits in one or more large bronchi with symptoms of bronchostenosis (3 cases). (3) Multiple deposits in the trachea and bronchi and, possibly, also in the parenchyma (11 cases). These patients had multiple stenoses with consequent respiratory embarrassment and a tendency to recurrent infections and hemoptysis. A study of the majority of reports showed that the larynx, trachea, and main bronchi were principally involved.2"5 Some patients have had bronchoscopic removal of obstructing masses projecting into the tracheobronchial tree at various levels from the glottis on down. 3 ' 5 In patients with parenchymal involvement, the disease generally has taken the form of multiple, bilateral nodules.6"9 On reviewing the literature in 1961, Lundin, Simonsson, and Winberg 6 were able to find 14 cases of amyloid tumor in the pulmonary parenchyma and 1 case in the pleura. A more detailed subclassification of pulmonary amyloidosis was put forward by Weiss 9 : I. Secondary amyloidosis. II. Senescent cardiac amyloidosis. III. Amyloidosis associated with myelomatosis. IV. Primary amyloidosis. A. Generalized primary amyloidosis. 1. Nodular pulmonary involvement. 2. Diffuse pulmonary involvement. B. Amyloidosis limited to the respiratory tract. 1. Upper respiratory tract and lungs. 2. Isolated nodular pulmonary amyloidosis. MYLOID
From The Genesee Hospital and The Department of Surgery of The University of Roch ester School of Medicine and Dentistry, Rochester, N. Y. Received for publication Oct. 14, 1964. 860
Vol. 49, No. 5
May. 1965
SOLITARY AMYLOID TUMOR
861
The 13 cases Weiss collected, including his own, belong to the final subclass listed above. Several of these are reports in which the diagnosis was made at autopsy. In 7 of the 13 cases there were multiple deposits distributed in both lungs. There were 9 men and 4 women, with an age range of 52 to 88 years (average 69.5 years). In the recent literature, there are additional scattered reports of patients in whom multiple amyloid tumors have been resected or enucleated. 10 ' lx Only three reports describe patients treated by pulmonary resections for solitary lesions of one lung. In all of these, a pneumonectomy was done. In the first case, fixation of the right hilum by the firm tumor mass neces sitated a pneumonectomy. 12 The second patient had the entire lung removed because he was suspected of having a malignant neoplasm of the right middle lobe.13 In the third case,14 a mass in the left upper lobe had extended across the interlobar fissure to involve the superior segment of the lower lobe. It was also adherent to the parietal pleura. A pneumonectomy was performed be cause the appearance was highly suspicious of a primary pulmonary cancer. It is interesting that some slightly enlarged hilar lymph nodes also showed amyloid deposits. The present case is unique in that a solitary, peripheral parenchymal amyloid tumor was found which could be removed by subsegmental resection. This case also fits into the category of isolated nodular pulmonary amyloidosis, as classified by Weiss.
Fig. 1.—Preoperative roentgenogram of the chest shows the solid parenchymal lesion in the right fourth anterior intercostal space which tripled in size in a period of 18 months. There is also evidence of old disease in the left lung with a small, ill-defined density in the left third anterior rib space and a calcified hilar node. These did not change during the period of obser vation.
GRAVER
862
J. Thoracic and Cardiovas. Surg.
CASE REPORT
The patient was a white, married woman, 61 years of age. One and one half years previous to hospitalization she had spit up approximately a cupful of blood. Two months later she had had a second episode of hemoptysis of about half this amount. In each instance, the blood was not brought up all at one time, but over a period of hours, a bit at a time. Since then, he had had occasional smaller episodes of hemoptysis: the last had occurred 2 months before the hospitalization. A chest roentgenogram made when hemoptysis had first occurred showed a nodular den sity, approximately 8 mm. in diameter, in the right lung field at the level of the fourth an terior rib space. A calcified lymph node was seen in the left hilum and a smaller, less welldefined density was present in the left lung field at the level of the third anterior rib space. The two pulmonary lesions were thought to have a nonspecific appearance and both were as sumed to be the result of an old inflammatory process. Following the second bout of hemoptysis, the patient was bronchoscoped and the findings were negative. During the subsequent 18 months, the lesion in the right lung tripled in diameter and appeared more substantial than it had initially (Fig. 1 ) . Tomograms showed it to have a roughly triangular shape without calcification and with a margin which was not crisply circumscribed (Fig. 2 ) . These characteristics led the first radiologist to believe that it might be a conglomeration of granulomatous lesions, although at this point he could not rule out neoplasm. Other radiologists thought it was malignant. The smaller lesion in the left lung had not changed and still has not grown during the period of observation which now totals over 34 months. Past History.—As a child, the patient had had a prolonged exposure to tuberculosis from her mother, who had developed tuberculosis 4 years prior to the patient's birth. She
Fig. 2.—A tomogTam of the right mid-lung- field shows the lesion most clearly 5.5 cm. up from the tabletop with the patient lying supine. It has a roughly triangular shape and does not contain any calcification.
was 10 years of age when her mother died. The patient had had bronchopneumonia at 45 years of age; she has never smoked tobacco. Review of Systems.—Review indicated only that she had had a hysterectomy performed at the time of removal of an ovarian cyst several years previously. Family History.—The patient had had 10 or 12 cousins who had died from some form of cancer. One brother died of metastatic cancer of the liver which may have started in the rectum. Physical Examination.—Physical examination did not reveal any pertinent abnormalities. The patient was admitted to The Genesee Hospital on Sept. 10, 1963. Hemoglobin was 12.1 Gm.; hematocrit, 40 per cent; white blood count 5,400, with a normal differential. Urinalysis was negative. A right scalene node biopsy revealed mild, nonspecific reticuloendothelial cell hyperplasia. Operation.—On Sept. 13, 1963, a right posterolateral thoracotomy was done. The nodule in the right lung lay 1 to 2 cm. beneath the pleural surface in the parenchyma of the lateral basal pulmonary segment. There was no enlargement of hilar or mediastinal lymph nodes. A subsegmental excision of the lesion with a margin of surrounding normal parenchyma was done. Pathologic Diagnosis.—A frozen section was obtained and the conclusion was reached that it was some unusual form of granuloma. Grossly, there was waxy material in the center which broke up and was difficult to section. The nodule was a poorly circumscribed, grayyellow mass, 2.5 cm. in greatest dimension. Paraffin sections revealed sheets of amorphous uniformly eosinophilic-staining material which obliterated the lung parenchyma in the central portions of the deposit, although blood vessels could be found within it. Moderate numbers of giant cells of the foreign body type were intimately associated with the homogeneous material (Fig. 3 ) . Thick trabeculae of fibrous tissue were haphazardly dispersed within the masses of amorphous material. The distribution and character of both the giant cells and the fibrous tissue was not at all characteristic of a tuberculous process. I n the periphery of
Pig. 4.—Section shows one of the isolated foci of basophilic staining- dystrophic bone associated with the uniformly eosinophilic staining material. (Hematoxylin and eosin ; X220.)
the lesion, there was cuboidal metaplasia of alveolar lining cells. Many of the alveolar septa showed moderate fibrous thickening. I n several isolated foci, there were small basophilic staining structures which resembled portions of dystrophic bony trabeculae (Fig. 4 ) . Stains with Congo red were clearly positive for amyloid. There was metachromasia demonstrable with crystal violet stain and a pale reaction with periodic acid-Schiff stain. All of these staining reactions are confirmatory for the presence of amyloid. A pathological diagnosis of "discrete, nodular, tumoral amyloidosis" was made by Dr. John N. Abbott.* Postoperative Course.—Additional laboratory studies were done in the postoperative period to help rule out diffuse amyloidosis. Ten cubic centimeters of 1 per cent Congo red was given with 79 per cent retention of dye in one hour. This is negative for amyloid dis ease. Serum protein electrophoresis was normal. Serum alkaline phosphatase was normal on two occasions (3.7 units and 2.6 Bodansky units). The Bromsulphalein retention was 2 per cent. The patient initially did well postoperatively and has not developed any new lesions during the 10 montlis she has been followed since then. However, on May 24, 1964, she again had an episode of hemoptysis which subsided within 3 days. She was otherwise asymptomatic and examination was unrevealing. Chest films showed only operative scarring in the right lower lobe area and persistence of the small lesion in the left upper lung field. She was hospitalized and bronchoscoped. No endobronchial tumor was found. Aspirated material for cell study and culture was negative. Biopsy of a small patch of mucosal reddening in the intermediate bronchus showed chronic bronchitis. A complete bilateral bronchogram of good quality was obtained. This confirmed that there was no endobronchial filling defect and no evidence of bronchiectasis. The patient continues to feel well and returned to work and full activity about a week after these procedures. •Director of Pathology, The Genesee Hospital, Rochester, New York.
Vol. 49, No. 5 May, I96S
SOLITAKY AMYLOID TTJMOB
865
DISCUSSION
Amyloidosis is a disease of uncertain etiology. The primary type has no known cause or predisposing factors. Secondary amyloidosis accompanies chronic infection or degenerative processes. The clinical picture depends principally upon the organs involved. Four subdivisions of amyloidosis were proposed by Reimann, Koucky, and Eklund 15 : I. Primary amyloidosis is usually diffuse and characterized by (a) absence of preceding disease, (b) no involvement of organs or tissue usually affected in the secondary form, (c) involvement of mesodermal tissue, cardiovascular sys tem, gastrointestinal tract, smooth and striated muscle, and lymph nodes, (d) variation in staining reactions, and (e) tendency to nodular deposits. II. Secondary amyloidosis usually follows chronic disease and is character ized by large deposits, especially in the spleen, liver, kidney, and adrenals, and by typical staining reaction. III. Amyloidosis occurring with multiple myeloma is also secondary in na ture but the distribution and character of the deposits frequently resemble those of the primary form except that huge deposits may occur in the joints and elsewhere. The spleen and liver are seldom involved. IV. Tumor-forming amyloidosis is characterized by the presence of small, solitary, or multiple tumor-like circumscribed foci confined to a single organ system, usually the respiratory tract or skin. It is usually of the primary type but is distinctive enough to be grouped separately. Amyloid deposits are chemically composed of a protein and a sulfatecontaining polysaccharide. Some investigators believe the latter is chondroitin sulfuric acid. Since the primary and secondary forms to some extent have dif ferent staining properties, it is conceivable that the composition of the deposits differs somewhat. Braunstein and Buerger 16 studied the histochemical and staining characteristics of several varieties of amyloid and concluded that three components are identifiable. In all types of amyloid, a protein content was prominent. They believed that most amyloid also contains two carbohy drates. One of these is probably glycoprotein and the other a nonsulfated acid mucopolysaccharide. However, they did not investigate any cases of amyloido sis in the respiratory tract. Pulmonary amyloid tumors may contain areas of cartilaginous metaplasia and calcification with or without ossification, as well as multinucleated giant cells.17 In the present case, there were moderate numbers of giant cells and scattered islands of bone formation (see Figs. 3 and 4). The postoperative laboratory tests were done to help rule out other unsus pected deposits or diffuse amyloidosis. When the disease is generalized, the serum electrophoresis may indicate a hyperglobulinemia. The normal result in the present case tends to exclude myeloma as well as amyloidosis. The serum alkaline phosphatase may be greatly elevated in this disease. Bromsulphalein retention is increased when there is liver involvement but was not high in this patient. The Congo red test was similarly normal in this patient. More may be removed from the serum (90 to 100 per cent) when the patient has wide spread amyloid deposits. Thus there is no evidence by physical or laboratory
CEAVEB
866
J. Thoracic and Cardiovas. Surg.
examination of amyloidosis elsewhere in the body of this patient. A suspicion remains, of course, that the small, poorly defined density in the contralateral lung may be a second amyloid lesion. However, its stability prior to surgery and throughout the follow-up period, as well as its proximity to a calcified hilar node, suggests it may be a healed granuloma. As of now, there is still no clear explanation of the episodes of hemoptysis. Originally they were thought to be related to the amyloid tumor in the right lung, but since bleeding occurred again 8 months following resection there must be some other cause. Continued close observation is necessary. As in most of the recorded cases of isolated nodular pulmonary amy loidosis, the patient in the case reported here had few symptoms. Some have had a cough, others have had hemoptysis, as did this woman. The more periph eral tumors are less likely to be accompanied by symptoms. A conclusive diagnosis could not be reached from the roentgenograms and concern lest a neoplasm be overlooked led to exploration. The present case presents an ex ample of what is certainly one of the rarer types of solitary pulmonary parenchymal nodules, one that is not likely to be thought of when a peripheral "coin" lesion is seen. This is how it presented, however, and, as a result, this lesion should be included in the differential diagnosis of solitary, circum scribed, pulmonary nodules. SUMMARY
Solitary tumor-like deposits of amyloid in the lungs are an unusual form of primary pulmonary amyloidosis. There are infrequent reports of patients in whom multiple parenchymal amyloid tumors have been resected or enucleated. In three instances, solitary deposits have been treated by pneumonectomy. A case of isolated nodular pulmonary amyloidosis is recorded which pre sented as a slowly growing peripheral "coin" lesion in a 61-year-old woman with hemoptysis. It was removed by subsegmental resection and no new lesions have developed in the 10 months since operation. Hemoptysis occurred again 8 months following removal of the tumor, but no definite source of bleeding could be found. REFERENCES
1. Prowse, C. B . : Amyloidosis of the Lower Respiratory Tract, Thorax 13: 308, 1958. 2. Kamberg, 8., Loitman, B. S., and Holtz, S.: Amyloidosis of the Tracheobronchial Tree, New England J. Med. 266: 587, 1962. 3. Sehottenfeld, A., Arnold, L. M., Gruhn, J. G., and Etess, A. D.: Localized Amyloid Deposition in t h e Lower Respiratory Tract, Am. J . Med. 1 1 : 770, 1951. 4. Shinoi, K., Shiraishi, IT., and Yahata, J . I.: Amyloid Tumor of the Trachea and Lung Resembling Bronchial Asthma, Dis. Chest 42: 442, 1962. 5. Whitwell, F . : Localized Amyloid Infiltrations of the Lower Respiratory Tract, Thorax 8: 309, 1953. 6. Lundin, P., Simonsson, B., and Winberg, T.: Pneumopleural Amyloid Tumor, Acta radiol. 55: 139, 1961. 7. Duke, M.: Tumoral Amyloidosis of the Lungs, Arch. P a t h . 67: 110, 1959. 8. Sappington, S. W., Davie, J. H., and Horneff, J . A.: P r i m a r y Amyloidosis of the Lungs, J. Lab. & Clin. Med. 27: 882, 1942. 9. Weiss, L.: Isolated Nodular Pulmonary Amyloidosis, Am. J. Clin. P a t h . 33: 318, 1960. 10. Bergman, F., and Linder, E . : Tumor-Forming Amyloidosis of the Lung, J . THORACIC SUKG. 35: 628,
1958.
Vol. 49, No. S
May. 1965
SOLITARY AMYLOID TUMOE
867 " '
11. SjJrensen, H. K.: P r i m a r y Isolated Nodular Amyloidosis of the Lung, Aeta chir. scandinav. (Suppl.) 283: 162, 1961. 12. Weismann, E. E., Clagett, O. T., and McDonald, J . E.: Amyloid Disease of the Lung Treated by Pneumonectomy, J. THORACIC SURG. 16: 269, 1947.
13. Haynes, A. L., Clagett, O. T., and McDonald, J . E . : Tumor Forming Amyloidosis of the Lung, Surgery 24: 120, 1948. 14. Schiiller, J., Bolin, H., and Linder, E.: Tumor Forming Amyloidosis of t h e Lower Respiratory System, Dis. Chest 42: 58, 1962. 15. Eeimann, H. A., Koucky, E. F., and Eklund, C. M.: P r i m a r y Amyloidosis Limited to Tissues of Mesodermal Origin, Am. J . P a t h , 1 1 : 977, 1935, 16. Braunstein, J., and Buerger, L . : A Study of the Histochemical Staining Characteristics of Amyloid, Am. J. P a t h . 35: 791, 1959. 17. Glauser, O.: t)ber tumorformiges Amvloid der Lungen, Schweiz. Ztschr. allg. P a t h . 18: 42, 1955.
L. Craver, M.D., Rochester, N.
Y.
A
tumors are not uncommon in the respiratory tract. Over 100 such cases have been recorded. However, these tumors rarely occur as an iso lated lesion in the pulmonary parenchyma. In 1958, Prowse 1 reviewed 18 cases which included 2 of his own. He divided them clinically into three groups: (1) Tumor-like deposits of amyloid in the lungs (4 cases). All patients were asymptomatic and had multiple nodules which were found incidentally at autopsy after death from an unrelated cause. (2) Amyloid deposits in one or more large bronchi with symptoms of bronchostenosis (3 cases). (3) Multiple deposits in the trachea and bronchi and, possibly, also in the parenchyma (11 cases). These patients had multiple stenoses with consequent respiratory embarrassment and a tendency to recurrent infections and hemoptysis. A study of the majority of reports showed that the larynx, trachea, and main bronchi were principally involved.2"5 Some patients have had bronchoscopic removal of obstructing masses projecting into the tracheobronchial tree at various levels from the glottis on down. 3 ' 5 In patients with parenchymal involvement, the disease generally has taken the form of multiple, bilateral nodules.6"9 On reviewing the literature in 1961, Lundin, Simonsson, and Winberg 6 were able to find 14 cases of amyloid tumor in the pulmonary parenchyma and 1 case in the pleura. A more detailed subclassification of pulmonary amyloidosis was put forward by Weiss 9 : I. Secondary amyloidosis. II. Senescent cardiac amyloidosis. III. Amyloidosis associated with myelomatosis. IV. Primary amyloidosis. A. Generalized primary amyloidosis. 1. Nodular pulmonary involvement. 2. Diffuse pulmonary involvement. B. Amyloidosis limited to the respiratory tract. 1. Upper respiratory tract and lungs. 2. Isolated nodular pulmonary amyloidosis. MYLOID
From The Genesee Hospital and The Department of Surgery of The University of Roch ester School of Medicine and Dentistry, Rochester, N. Y. Received for publication Oct. 14, 1964. 860
Vol. 49, No. 5
May. 1965
SOLITARY AMYLOID TUMOR
861
The 13 cases Weiss collected, including his own, belong to the final subclass listed above. Several of these are reports in which the diagnosis was made at autopsy. In 7 of the 13 cases there were multiple deposits distributed in both lungs. There were 9 men and 4 women, with an age range of 52 to 88 years (average 69.5 years). In the recent literature, there are additional scattered reports of patients in whom multiple amyloid tumors have been resected or enucleated. 10 ' lx Only three reports describe patients treated by pulmonary resections for solitary lesions of one lung. In all of these, a pneumonectomy was done. In the first case, fixation of the right hilum by the firm tumor mass neces sitated a pneumonectomy. 12 The second patient had the entire lung removed because he was suspected of having a malignant neoplasm of the right middle lobe.13 In the third case,14 a mass in the left upper lobe had extended across the interlobar fissure to involve the superior segment of the lower lobe. It was also adherent to the parietal pleura. A pneumonectomy was performed be cause the appearance was highly suspicious of a primary pulmonary cancer. It is interesting that some slightly enlarged hilar lymph nodes also showed amyloid deposits. The present case is unique in that a solitary, peripheral parenchymal amyloid tumor was found which could be removed by subsegmental resection. This case also fits into the category of isolated nodular pulmonary amyloidosis, as classified by Weiss.
Fig. 1.—Preoperative roentgenogram of the chest shows the solid parenchymal lesion in the right fourth anterior intercostal space which tripled in size in a period of 18 months. There is also evidence of old disease in the left lung with a small, ill-defined density in the left third anterior rib space and a calcified hilar node. These did not change during the period of obser vation.
GRAVER
862
J. Thoracic and Cardiovas. Surg.
CASE REPORT
The patient was a white, married woman, 61 years of age. One and one half years previous to hospitalization she had spit up approximately a cupful of blood. Two months later she had had a second episode of hemoptysis of about half this amount. In each instance, the blood was not brought up all at one time, but over a period of hours, a bit at a time. Since then, he had had occasional smaller episodes of hemoptysis: the last had occurred 2 months before the hospitalization. A chest roentgenogram made when hemoptysis had first occurred showed a nodular den sity, approximately 8 mm. in diameter, in the right lung field at the level of the fourth an terior rib space. A calcified lymph node was seen in the left hilum and a smaller, less welldefined density was present in the left lung field at the level of the third anterior rib space. The two pulmonary lesions were thought to have a nonspecific appearance and both were as sumed to be the result of an old inflammatory process. Following the second bout of hemoptysis, the patient was bronchoscoped and the findings were negative. During the subsequent 18 months, the lesion in the right lung tripled in diameter and appeared more substantial than it had initially (Fig. 1 ) . Tomograms showed it to have a roughly triangular shape without calcification and with a margin which was not crisply circumscribed (Fig. 2 ) . These characteristics led the first radiologist to believe that it might be a conglomeration of granulomatous lesions, although at this point he could not rule out neoplasm. Other radiologists thought it was malignant. The smaller lesion in the left lung had not changed and still has not grown during the period of observation which now totals over 34 months. Past History.—As a child, the patient had had a prolonged exposure to tuberculosis from her mother, who had developed tuberculosis 4 years prior to the patient's birth. She
Fig. 2.—A tomogTam of the right mid-lung- field shows the lesion most clearly 5.5 cm. up from the tabletop with the patient lying supine. It has a roughly triangular shape and does not contain any calcification.
was 10 years of age when her mother died. The patient had had bronchopneumonia at 45 years of age; she has never smoked tobacco. Review of Systems.—Review indicated only that she had had a hysterectomy performed at the time of removal of an ovarian cyst several years previously. Family History.—The patient had had 10 or 12 cousins who had died from some form of cancer. One brother died of metastatic cancer of the liver which may have started in the rectum. Physical Examination.—Physical examination did not reveal any pertinent abnormalities. The patient was admitted to The Genesee Hospital on Sept. 10, 1963. Hemoglobin was 12.1 Gm.; hematocrit, 40 per cent; white blood count 5,400, with a normal differential. Urinalysis was negative. A right scalene node biopsy revealed mild, nonspecific reticuloendothelial cell hyperplasia. Operation.—On Sept. 13, 1963, a right posterolateral thoracotomy was done. The nodule in the right lung lay 1 to 2 cm. beneath the pleural surface in the parenchyma of the lateral basal pulmonary segment. There was no enlargement of hilar or mediastinal lymph nodes. A subsegmental excision of the lesion with a margin of surrounding normal parenchyma was done. Pathologic Diagnosis.—A frozen section was obtained and the conclusion was reached that it was some unusual form of granuloma. Grossly, there was waxy material in the center which broke up and was difficult to section. The nodule was a poorly circumscribed, grayyellow mass, 2.5 cm. in greatest dimension. Paraffin sections revealed sheets of amorphous uniformly eosinophilic-staining material which obliterated the lung parenchyma in the central portions of the deposit, although blood vessels could be found within it. Moderate numbers of giant cells of the foreign body type were intimately associated with the homogeneous material (Fig. 3 ) . Thick trabeculae of fibrous tissue were haphazardly dispersed within the masses of amorphous material. The distribution and character of both the giant cells and the fibrous tissue was not at all characteristic of a tuberculous process. I n the periphery of
Pig. 4.—Section shows one of the isolated foci of basophilic staining- dystrophic bone associated with the uniformly eosinophilic staining material. (Hematoxylin and eosin ; X220.)
the lesion, there was cuboidal metaplasia of alveolar lining cells. Many of the alveolar septa showed moderate fibrous thickening. I n several isolated foci, there were small basophilic staining structures which resembled portions of dystrophic bony trabeculae (Fig. 4 ) . Stains with Congo red were clearly positive for amyloid. There was metachromasia demonstrable with crystal violet stain and a pale reaction with periodic acid-Schiff stain. All of these staining reactions are confirmatory for the presence of amyloid. A pathological diagnosis of "discrete, nodular, tumoral amyloidosis" was made by Dr. John N. Abbott.* Postoperative Course.—Additional laboratory studies were done in the postoperative period to help rule out diffuse amyloidosis. Ten cubic centimeters of 1 per cent Congo red was given with 79 per cent retention of dye in one hour. This is negative for amyloid dis ease. Serum protein electrophoresis was normal. Serum alkaline phosphatase was normal on two occasions (3.7 units and 2.6 Bodansky units). The Bromsulphalein retention was 2 per cent. The patient initially did well postoperatively and has not developed any new lesions during the 10 montlis she has been followed since then. However, on May 24, 1964, she again had an episode of hemoptysis which subsided within 3 days. She was otherwise asymptomatic and examination was unrevealing. Chest films showed only operative scarring in the right lower lobe area and persistence of the small lesion in the left upper lung field. She was hospitalized and bronchoscoped. No endobronchial tumor was found. Aspirated material for cell study and culture was negative. Biopsy of a small patch of mucosal reddening in the intermediate bronchus showed chronic bronchitis. A complete bilateral bronchogram of good quality was obtained. This confirmed that there was no endobronchial filling defect and no evidence of bronchiectasis. The patient continues to feel well and returned to work and full activity about a week after these procedures. •Director of Pathology, The Genesee Hospital, Rochester, New York.
Vol. 49, No. 5 May, I96S
SOLITAKY AMYLOID TTJMOB
865
DISCUSSION
Amyloidosis is a disease of uncertain etiology. The primary type has no known cause or predisposing factors. Secondary amyloidosis accompanies chronic infection or degenerative processes. The clinical picture depends principally upon the organs involved. Four subdivisions of amyloidosis were proposed by Reimann, Koucky, and Eklund 15 : I. Primary amyloidosis is usually diffuse and characterized by (a) absence of preceding disease, (b) no involvement of organs or tissue usually affected in the secondary form, (c) involvement of mesodermal tissue, cardiovascular sys tem, gastrointestinal tract, smooth and striated muscle, and lymph nodes, (d) variation in staining reactions, and (e) tendency to nodular deposits. II. Secondary amyloidosis usually follows chronic disease and is character ized by large deposits, especially in the spleen, liver, kidney, and adrenals, and by typical staining reaction. III. Amyloidosis occurring with multiple myeloma is also secondary in na ture but the distribution and character of the deposits frequently resemble those of the primary form except that huge deposits may occur in the joints and elsewhere. The spleen and liver are seldom involved. IV. Tumor-forming amyloidosis is characterized by the presence of small, solitary, or multiple tumor-like circumscribed foci confined to a single organ system, usually the respiratory tract or skin. It is usually of the primary type but is distinctive enough to be grouped separately. Amyloid deposits are chemically composed of a protein and a sulfatecontaining polysaccharide. Some investigators believe the latter is chondroitin sulfuric acid. Since the primary and secondary forms to some extent have dif ferent staining properties, it is conceivable that the composition of the deposits differs somewhat. Braunstein and Buerger 16 studied the histochemical and staining characteristics of several varieties of amyloid and concluded that three components are identifiable. In all types of amyloid, a protein content was prominent. They believed that most amyloid also contains two carbohy drates. One of these is probably glycoprotein and the other a nonsulfated acid mucopolysaccharide. However, they did not investigate any cases of amyloido sis in the respiratory tract. Pulmonary amyloid tumors may contain areas of cartilaginous metaplasia and calcification with or without ossification, as well as multinucleated giant cells.17 In the present case, there were moderate numbers of giant cells and scattered islands of bone formation (see Figs. 3 and 4). The postoperative laboratory tests were done to help rule out other unsus pected deposits or diffuse amyloidosis. When the disease is generalized, the serum electrophoresis may indicate a hyperglobulinemia. The normal result in the present case tends to exclude myeloma as well as amyloidosis. The serum alkaline phosphatase may be greatly elevated in this disease. Bromsulphalein retention is increased when there is liver involvement but was not high in this patient. The Congo red test was similarly normal in this patient. More may be removed from the serum (90 to 100 per cent) when the patient has wide spread amyloid deposits. Thus there is no evidence by physical or laboratory
CEAVEB
866
J. Thoracic and Cardiovas. Surg.
examination of amyloidosis elsewhere in the body of this patient. A suspicion remains, of course, that the small, poorly defined density in the contralateral lung may be a second amyloid lesion. However, its stability prior to surgery and throughout the follow-up period, as well as its proximity to a calcified hilar node, suggests it may be a healed granuloma. As of now, there is still no clear explanation of the episodes of hemoptysis. Originally they were thought to be related to the amyloid tumor in the right lung, but since bleeding occurred again 8 months following resection there must be some other cause. Continued close observation is necessary. As in most of the recorded cases of isolated nodular pulmonary amy loidosis, the patient in the case reported here had few symptoms. Some have had a cough, others have had hemoptysis, as did this woman. The more periph eral tumors are less likely to be accompanied by symptoms. A conclusive diagnosis could not be reached from the roentgenograms and concern lest a neoplasm be overlooked led to exploration. The present case presents an ex ample of what is certainly one of the rarer types of solitary pulmonary parenchymal nodules, one that is not likely to be thought of when a peripheral "coin" lesion is seen. This is how it presented, however, and, as a result, this lesion should be included in the differential diagnosis of solitary, circum scribed, pulmonary nodules. SUMMARY
Solitary tumor-like deposits of amyloid in the lungs are an unusual form of primary pulmonary amyloidosis. There are infrequent reports of patients in whom multiple parenchymal amyloid tumors have been resected or enucleated. In three instances, solitary deposits have been treated by pneumonectomy. A case of isolated nodular pulmonary amyloidosis is recorded which pre sented as a slowly growing peripheral "coin" lesion in a 61-year-old woman with hemoptysis. It was removed by subsegmental resection and no new lesions have developed in the 10 months since operation. Hemoptysis occurred again 8 months following removal of the tumor, but no definite source of bleeding could be found. REFERENCES
1. Prowse, C. B . : Amyloidosis of the Lower Respiratory Tract, Thorax 13: 308, 1958. 2. Kamberg, 8., Loitman, B. S., and Holtz, S.: Amyloidosis of the Tracheobronchial Tree, New England J. Med. 266: 587, 1962. 3. Sehottenfeld, A., Arnold, L. M., Gruhn, J. G., and Etess, A. D.: Localized Amyloid Deposition in t h e Lower Respiratory Tract, Am. J . Med. 1 1 : 770, 1951. 4. Shinoi, K., Shiraishi, IT., and Yahata, J . I.: Amyloid Tumor of the Trachea and Lung Resembling Bronchial Asthma, Dis. Chest 42: 442, 1962. 5. Whitwell, F . : Localized Amyloid Infiltrations of the Lower Respiratory Tract, Thorax 8: 309, 1953. 6. Lundin, P., Simonsson, B., and Winberg, T.: Pneumopleural Amyloid Tumor, Acta radiol. 55: 139, 1961. 7. Duke, M.: Tumoral Amyloidosis of the Lungs, Arch. P a t h . 67: 110, 1959. 8. Sappington, S. W., Davie, J. H., and Horneff, J . A.: P r i m a r y Amyloidosis of the Lungs, J. Lab. & Clin. Med. 27: 882, 1942. 9. Weiss, L.: Isolated Nodular Pulmonary Amyloidosis, Am. J. Clin. P a t h . 33: 318, 1960. 10. Bergman, F., and Linder, E . : Tumor-Forming Amyloidosis of the Lung, J . THORACIC SUKG. 35: 628,
1958.
Vol. 49, No. S
May. 1965
SOLITARY AMYLOID TUMOE
867 " '
11. SjJrensen, H. K.: P r i m a r y Isolated Nodular Amyloidosis of the Lung, Aeta chir. scandinav. (Suppl.) 283: 162, 1961. 12. Weismann, E. E., Clagett, O. T., and McDonald, J . E.: Amyloid Disease of the Lung Treated by Pneumonectomy, J. THORACIC SURG. 16: 269, 1947.
13. Haynes, A. L., Clagett, O. T., and McDonald, J . E . : Tumor Forming Amyloidosis of the Lung, Surgery 24: 120, 1948. 14. Schiiller, J., Bolin, H., and Linder, E.: Tumor Forming Amyloidosis of t h e Lower Respiratory System, Dis. Chest 42: 58, 1962. 15. Eeimann, H. A., Koucky, E. F., and Eklund, C. M.: P r i m a r y Amyloidosis Limited to Tissues of Mesodermal Origin, Am. J . P a t h , 1 1 : 977, 1935, 16. Braunstein, J., and Buerger, L . : A Study of the Histochemical Staining Characteristics of Amyloid, Am. J. P a t h . 35: 791, 1959. 17. Glauser, O.: t)ber tumorformiges Amvloid der Lungen, Schweiz. Ztschr. allg. P a t h . 18: 42, 1955.