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Primary Reticulum Cell Sarcoma of the Lung with Endobronchial Involvement
Primary Reticulum Cell Sarcoma of the Lung with Endobronchial Involvement Case Report MILTON
B.
KRESS, M.D., F.C.C.P.* AND JOHN H. HIRSCHFELD, M.D., F.C.C.P.
Baltimore, Maryland
E
NDOBRONCHIAL INVASION BY PRIMARY
malignant lymphoma has been considered an uncommon manifestation of the disease. 1 Although primary lymphoma of the lung does not begin as an intraluminal mass, the presence of a mass on bronchoscopic examination has been reported occasionally and bronchoscopic aberrations are not infrequently discovered. t •3 Of the lymphomas listed as primary reticulum cell sarcoma of the lung, however, a positive diagnosis of malignancy on bronchoscopic biopsy has been made in only three cases. t.4 Cytologic findings of the sputum and bronchial washings in primary malignant lymphoma of the lung have also occasionally been reported as being positive for malignancy,' but in one series of 16 patients so studied, including two patients with reticulum cell sarcoma, all were reported as negative.' * Assistant ProCessor of Medicine, The Johns Hop-
The case herein described is of interest in that the diagnosis of malignancy was made from cytologic examination of the sputum and a positive diagnosis of reticulum cell sarcoma was made from tissue removed on bronchoscopic biopsy. CASE HISTORY
This patient, a 64-year.old white man, was treated by his physician in August of 1960 for an upper respiratory infection. A routine chest roentgenogram was normal. His symptoms dis· appeared after several injections of penicil\in and medication for his cough. His weight at this time was recorded as 230 pounds. During the next few months, he noted progressive weight loss without following any prescribed diet. On December 24, 1960, he became quite dyspneic on climbing a flight of stairs and on December 26, he expectorated mucoid sputum flecked with blood. His temperature rose to 101· F. and he was treated with medications, including an antibiotic, but his symptoms persisted. A chest roentgenogram January 6, 1961 showed a pneumonic process in the left lower lobe (Fig.
tAl·
kins University School oC Medicine.
FIG. IA FIG. IB IA: January 6, 1961, pneumonic process leCt mid·lung, lower lobe. FIGURE IB: January 24, 1961. pleural effusion obscuring pneumonic process, cardiac shadow enlarged due to pericardial effusion.
FIGURE
436
Volume 4'. No.4 April 1964
PRIMARY RETICULUM SARCOMA OF LUNG
437
He was admitted to the Church Home and Hospital January 17, 1961 for further therapy. His weight was 175 pounds, a loss of 55 pounds since August of 1960. He complained of only minimal cough and expectoration, but had mod· erate dyspnea. On physical examination, there was marked impairment of percussion noted throughout the left lung. The diaphragm did not move on the left and there were a few rales over the anterior left chest. The breath sounds were absent at the left base posteriorly and distant over the apex anteriorly. A to-and-fro murmur which was heard from the apex of the heart to the sternum was considered due to a pericardial friction rub. His temperature was elevated to 102° F. and for the next two weeks varied from 100° to 103° F. The pulse varied from 80 to 120 and the respirations from 20 to 30. Laboratory Studies and X-ray Examinations: Examination of the blood revealed a normal white cell count and hematocrit. Sputum studies for tubercle bacilli and other pathogenic organisms were negative. The PPD and histoplasmin skin tests were also negative.
At the time of admission on January 17, 1961, roentgenograms of the chest showed consolidation of the lower two-thirds of the left lung, thought to be due to a pneumonic process with a superimposed pleural effusion. The cardiac shadow was somewhat increased in size due to a pericardia I effusion. An x-ray film taken on January 24. 1961 showed an increase in the left pleural effusion (Fig. I B) and 1100 ml. of clear, fibrinous, straw-colored fluid was removed. This fluid proved to be negative for malignant cells and for organisms on culture. Sputum examination on smear and culture was also negative for bacteria. On repeat thoracentesis on January 26, several attempts to withdraw fluid were unsuccessful. In the meantime, the patient's temperature had not responded to broad spectrum antibiotics. Cytologic examination of sputum at this time revealed cells which were considered com· patible with either lymphosarcoma or small cell carcinoma (Fig. 2). On January 31, 1961, bronchoscopy revealed a granular mass in the left mainstem bronchus 2 em. below the carina producing substantial obstruction of the bronchus. This mass bled profusely when biopsied and microscopic examination of the biopsy material FIGURE Ie (upper): February 8, 1961, clearing of pleural effusion, pneumonic process and reduction in cardiac size to normal after nitrogen mustard therapy. FIGURE ID (center): April I, 1961, symmetrically enlarged mediastinal shadow with insignificant changes in the parenchymal infiltration, left upper and mid-lung. FtGURE IE (lower) : April 26, 1961, decrease in mediastinal enlargement to normal after x-ray therapy.
Diseases of
KRESS AND HIRSCHFELD
FIGURE 2: (January 2, 1961) Cytologic examination of cells from sputum stained with Papanicolaou stain showing malignant cells compatible with either small cell carcinoma or lymphoma. The loose and individual arrangement strongly suggest a lymphoma. The criteria for malignancy are a high nucleo-cytoplasmic ratio, chromatin clumping and abnormal pattern, prominent and irregular nucleoli, and nuclear molding (xIOOO). revealed a lymphosarcoma of the reticulum cell type (Figs. 3A and 3B). Over a three-day period, beginning February 4, 1961, the patient was given a total of 32 mg. of nitrogen mustard intravenously. On February 8, his temperature had returned to normal and within 48 hours, breath sounds could be heard clearly at the left base. The patient had no untoward reaction to the nitrogen mustard and x-ray films taken February 8. 1961 showed a pronounced decrease in the heart size in comparison with previous films, and marked clearing of the pleural changes, as well as the parenchymal changes of the left lung (Fig. IC). No discrete masses were seen, but residual fibrotic lesions were present in the left lung. The patient was much improved clinically and was discharged from the hospital February 9. 1901. After leaving the hospital, he did well for several weeks, but then again began to lose weight, cough, and complain of dyspnea. A roentgenogram taken April I, 1961 showed a slight increase in pleural reaction in the left base with minimal changes in the parenchymal densities in the left upper and mid lung fields, and symmetrical enlargement of the upper mediastinum (Fig. ID). He was given 32 mg. of nitrogen mustard, but on this occasion showed little or no response to chemotherapy. It was therefore decided to treat the patient with x-ray therapy. This was begun at the Johns Hopkins Hospital on April 10, 1961 and a total of 1900 r tumor dose was given in ten dose increments. Treatment was discontinued April 21, 1961 because of a drop in the platelet count to 88,000. A chest roentgenogram April 26 showed a decrease in the width of the mediastinum from 8.8 to 7.0
the Chest
em. (Fig. IE), but despite the improvement shown on the chest x-ray film, the patient had become weaker and continued to pursue a downhill course. On May I, 1961, the patient was confined to bed at home and on May 8, he was readmitted to Church Home and Hospital in a coma. He was found to be markedly tachypneic and respirations were 32 to 36. The blood pressure was 30/0 with no radial pulse. There was edema of the lower extremities, cyanosis of the finger tips, and signs of dullness in the left chest. He was given vasopressors and subjected to nasopharyngeal suction. He seemed to improve and became a little more responsive after the vasopressors. His blood pressure rose to 110/60, but he suddenly expired the following day, May 9, 1961. Permission for necropsy was not granted. DISCUSSION
The interesting feature of the present case was the finding of a granular mass in the bronchus which had the appearance of bronchogenic carcinoma, but which, on
FIGURE 3A (upper): (January 31, 1961) Hematoxylin and eosin stain of section of bronchial biopsy diagnosed as reticulum cell sarcoma (x400). FIGURE 3B (lower): (January 31, 1961) Silver methenamine stain showing marked proliferation of reticulum fibers with cells attached to fibers resembling "pussy willows" (x400).
Volume 45, No.4 April 1964
439
PRIMARY RETICULUM SARCOMA OF LUNG
microscopic section of biopsy material from the bronchial mass, was diagnosed as lymphosarcoma of the reticulum cell type. The finding of such a bronchial lesion in primary reticulum cell sarcoma of the lung has been reported in only three previous cases. I •4 However, since difficulty in differentiating lymphosarcoma of the lymphoid and reticulum cell type from small cell carcinoma on microscopic examination is frequently encountered,I,4-1 we followed the technique of Schiitz and Kohn4 to distinguish these tumors. They described a characteristic histologic pattern in reticulum cell sarcoma which consisted of marked proliferation of the reticulum fibers with the cells attached to the fibers in an arrangement which resembled "pussy willows." This pattern was best demonstrated when sections were stained for reticulum with silver methenamine and microscopic sections of the bronchoscopic biopsy material in the present case conformed to this pattern. In bronchogenic carcinoma and lymphoma of the small cell types, one finds sparse reticulum fibers separating large collections of cells; however, in bronchogenic carcinoma there is considerable variation from one part of the tumor to the other. The diagnosis in the present case was further substantiated, we believe, by the impressive response to the first course of nitrogen mustard. In this patient the parenchymal tumor, pleural effusion and pericardial effusion showed remarkable clearing after 0.4 mg./kg. (32 mg.) of nitrogen mustard had been given intravenously. The temperature returned to normal 24 hours
following completion of nitrogen mustard therapy after having ranged from 100° to 103 F. for several weeks. We believe such a response is highly unlikely in bronchogenic carcinoma. 0
It has been stated that the diagnosis of a primary lymphoma of the lung requires direct examination to confirm the fact that the lymphoma is predominantly in the lung rather than the mediastinal structures.While direct examination was not possible in the present case since thoracotomy was not done, we believe evidence for primary involvement of the lung was indicated by the fact that at the onset of the illness there was a pneumonic process in the left lower lobe with no evidence of mediastinal or general glandular involvement; nor was there any evidence of subsequent general glandular enlargement. REFERENCES
1 ROSE, A. H.: "Primary Lymphosarcoma of the Lung," ]. Thor. Surg., 33: 254, 1957. 2 BERGHUIS, J., CLAGETT, O. T. AND HARRISON, E. G., JR.: "The Surgical Treatment of Primary Malignant Lymphoma of the Lung,"
Dis. Chest, 40:29, 1961.
3 HALL, E. R., JR. AND BLADES, B.: "Primary Lymphosarcoma of the Lung," Dis. Chest, 36: 571, 1959. 4 SCHUTZ, W. AND KOHN, K.: uDas Primare Retothelsarkom der Lunge," Thoraxchirurgie,
4: 272, 1956. 5 KRESS, M. B. AND BRANTIGAN, O. C.: "Primary Lymphosarcoma of the Lung," Ann. Int. Med., 55:582, 1961. 6 BARON, M. G. AND WHITEHOUSE, W. M.: "Primary Lymphosarcoma of the Lung," Am. ]. Roentgenol., 85: 294, 1961. 7 SAMUELS, M. L., HOWE, C. B., DODD, G. D., JR., FULLER, L. M., SHULLENBERGER, C. C. AND LEARY, W. L.: "Endobronchial Malignant Lymphoma," Am. ]. Roentgenol., 85: 87, 1961.
FATAL CORONARY-ARTERY EMBOLISM AFTER RESECTION A case of thrombosis In a ligated pulmonary vein stump and subsequent fatal coronary artery embollsm after pulmonary resection for bronchogenic carcinoma Is presented. Although this appears to be an unusual complication of pulmonary resection, It Is suggested that further cases may be discovered
by awareness of this diagnostic posslbillty and careful anatomic study at postmortem examination. ). D. AND PEASLEY, E. D.: "Fatal Coronary Artery Embolism after Pulmonary Resection, Ntw Engl. ]. Med., 268:1444, 1963.
SPRINKLE,
Of
B.
KRESS, M.D., F.C.C.P.* AND JOHN H. HIRSCHFELD, M.D., F.C.C.P.
Baltimore, Maryland
E
NDOBRONCHIAL INVASION BY PRIMARY
malignant lymphoma has been considered an uncommon manifestation of the disease. 1 Although primary lymphoma of the lung does not begin as an intraluminal mass, the presence of a mass on bronchoscopic examination has been reported occasionally and bronchoscopic aberrations are not infrequently discovered. t •3 Of the lymphomas listed as primary reticulum cell sarcoma of the lung, however, a positive diagnosis of malignancy on bronchoscopic biopsy has been made in only three cases. t.4 Cytologic findings of the sputum and bronchial washings in primary malignant lymphoma of the lung have also occasionally been reported as being positive for malignancy,' but in one series of 16 patients so studied, including two patients with reticulum cell sarcoma, all were reported as negative.' * Assistant ProCessor of Medicine, The Johns Hop-
The case herein described is of interest in that the diagnosis of malignancy was made from cytologic examination of the sputum and a positive diagnosis of reticulum cell sarcoma was made from tissue removed on bronchoscopic biopsy. CASE HISTORY
This patient, a 64-year.old white man, was treated by his physician in August of 1960 for an upper respiratory infection. A routine chest roentgenogram was normal. His symptoms dis· appeared after several injections of penicil\in and medication for his cough. His weight at this time was recorded as 230 pounds. During the next few months, he noted progressive weight loss without following any prescribed diet. On December 24, 1960, he became quite dyspneic on climbing a flight of stairs and on December 26, he expectorated mucoid sputum flecked with blood. His temperature rose to 101· F. and he was treated with medications, including an antibiotic, but his symptoms persisted. A chest roentgenogram January 6, 1961 showed a pneumonic process in the left lower lobe (Fig.
tAl·
kins University School oC Medicine.
FIG. IA FIG. IB IA: January 6, 1961, pneumonic process leCt mid·lung, lower lobe. FIGURE IB: January 24, 1961. pleural effusion obscuring pneumonic process, cardiac shadow enlarged due to pericardial effusion.
FIGURE
436
Volume 4'. No.4 April 1964
PRIMARY RETICULUM SARCOMA OF LUNG
437
He was admitted to the Church Home and Hospital January 17, 1961 for further therapy. His weight was 175 pounds, a loss of 55 pounds since August of 1960. He complained of only minimal cough and expectoration, but had mod· erate dyspnea. On physical examination, there was marked impairment of percussion noted throughout the left lung. The diaphragm did not move on the left and there were a few rales over the anterior left chest. The breath sounds were absent at the left base posteriorly and distant over the apex anteriorly. A to-and-fro murmur which was heard from the apex of the heart to the sternum was considered due to a pericardial friction rub. His temperature was elevated to 102° F. and for the next two weeks varied from 100° to 103° F. The pulse varied from 80 to 120 and the respirations from 20 to 30. Laboratory Studies and X-ray Examinations: Examination of the blood revealed a normal white cell count and hematocrit. Sputum studies for tubercle bacilli and other pathogenic organisms were negative. The PPD and histoplasmin skin tests were also negative.
At the time of admission on January 17, 1961, roentgenograms of the chest showed consolidation of the lower two-thirds of the left lung, thought to be due to a pneumonic process with a superimposed pleural effusion. The cardiac shadow was somewhat increased in size due to a pericardia I effusion. An x-ray film taken on January 24. 1961 showed an increase in the left pleural effusion (Fig. I B) and 1100 ml. of clear, fibrinous, straw-colored fluid was removed. This fluid proved to be negative for malignant cells and for organisms on culture. Sputum examination on smear and culture was also negative for bacteria. On repeat thoracentesis on January 26, several attempts to withdraw fluid were unsuccessful. In the meantime, the patient's temperature had not responded to broad spectrum antibiotics. Cytologic examination of sputum at this time revealed cells which were considered com· patible with either lymphosarcoma or small cell carcinoma (Fig. 2). On January 31, 1961, bronchoscopy revealed a granular mass in the left mainstem bronchus 2 em. below the carina producing substantial obstruction of the bronchus. This mass bled profusely when biopsied and microscopic examination of the biopsy material FIGURE Ie (upper): February 8, 1961, clearing of pleural effusion, pneumonic process and reduction in cardiac size to normal after nitrogen mustard therapy. FIGURE ID (center): April I, 1961, symmetrically enlarged mediastinal shadow with insignificant changes in the parenchymal infiltration, left upper and mid-lung. FtGURE IE (lower) : April 26, 1961, decrease in mediastinal enlargement to normal after x-ray therapy.
Diseases of
KRESS AND HIRSCHFELD
FIGURE 2: (January 2, 1961) Cytologic examination of cells from sputum stained with Papanicolaou stain showing malignant cells compatible with either small cell carcinoma or lymphoma. The loose and individual arrangement strongly suggest a lymphoma. The criteria for malignancy are a high nucleo-cytoplasmic ratio, chromatin clumping and abnormal pattern, prominent and irregular nucleoli, and nuclear molding (xIOOO). revealed a lymphosarcoma of the reticulum cell type (Figs. 3A and 3B). Over a three-day period, beginning February 4, 1961, the patient was given a total of 32 mg. of nitrogen mustard intravenously. On February 8, his temperature had returned to normal and within 48 hours, breath sounds could be heard clearly at the left base. The patient had no untoward reaction to the nitrogen mustard and x-ray films taken February 8. 1961 showed a pronounced decrease in the heart size in comparison with previous films, and marked clearing of the pleural changes, as well as the parenchymal changes of the left lung (Fig. IC). No discrete masses were seen, but residual fibrotic lesions were present in the left lung. The patient was much improved clinically and was discharged from the hospital February 9. 1901. After leaving the hospital, he did well for several weeks, but then again began to lose weight, cough, and complain of dyspnea. A roentgenogram taken April I, 1961 showed a slight increase in pleural reaction in the left base with minimal changes in the parenchymal densities in the left upper and mid lung fields, and symmetrical enlargement of the upper mediastinum (Fig. ID). He was given 32 mg. of nitrogen mustard, but on this occasion showed little or no response to chemotherapy. It was therefore decided to treat the patient with x-ray therapy. This was begun at the Johns Hopkins Hospital on April 10, 1961 and a total of 1900 r tumor dose was given in ten dose increments. Treatment was discontinued April 21, 1961 because of a drop in the platelet count to 88,000. A chest roentgenogram April 26 showed a decrease in the width of the mediastinum from 8.8 to 7.0
the Chest
em. (Fig. IE), but despite the improvement shown on the chest x-ray film, the patient had become weaker and continued to pursue a downhill course. On May I, 1961, the patient was confined to bed at home and on May 8, he was readmitted to Church Home and Hospital in a coma. He was found to be markedly tachypneic and respirations were 32 to 36. The blood pressure was 30/0 with no radial pulse. There was edema of the lower extremities, cyanosis of the finger tips, and signs of dullness in the left chest. He was given vasopressors and subjected to nasopharyngeal suction. He seemed to improve and became a little more responsive after the vasopressors. His blood pressure rose to 110/60, but he suddenly expired the following day, May 9, 1961. Permission for necropsy was not granted. DISCUSSION
The interesting feature of the present case was the finding of a granular mass in the bronchus which had the appearance of bronchogenic carcinoma, but which, on
FIGURE 3A (upper): (January 31, 1961) Hematoxylin and eosin stain of section of bronchial biopsy diagnosed as reticulum cell sarcoma (x400). FIGURE 3B (lower): (January 31, 1961) Silver methenamine stain showing marked proliferation of reticulum fibers with cells attached to fibers resembling "pussy willows" (x400).
Volume 45, No.4 April 1964
439
PRIMARY RETICULUM SARCOMA OF LUNG
microscopic section of biopsy material from the bronchial mass, was diagnosed as lymphosarcoma of the reticulum cell type. The finding of such a bronchial lesion in primary reticulum cell sarcoma of the lung has been reported in only three previous cases. I •4 However, since difficulty in differentiating lymphosarcoma of the lymphoid and reticulum cell type from small cell carcinoma on microscopic examination is frequently encountered,I,4-1 we followed the technique of Schiitz and Kohn4 to distinguish these tumors. They described a characteristic histologic pattern in reticulum cell sarcoma which consisted of marked proliferation of the reticulum fibers with the cells attached to the fibers in an arrangement which resembled "pussy willows." This pattern was best demonstrated when sections were stained for reticulum with silver methenamine and microscopic sections of the bronchoscopic biopsy material in the present case conformed to this pattern. In bronchogenic carcinoma and lymphoma of the small cell types, one finds sparse reticulum fibers separating large collections of cells; however, in bronchogenic carcinoma there is considerable variation from one part of the tumor to the other. The diagnosis in the present case was further substantiated, we believe, by the impressive response to the first course of nitrogen mustard. In this patient the parenchymal tumor, pleural effusion and pericardial effusion showed remarkable clearing after 0.4 mg./kg. (32 mg.) of nitrogen mustard had been given intravenously. The temperature returned to normal 24 hours
following completion of nitrogen mustard therapy after having ranged from 100° to 103 F. for several weeks. We believe such a response is highly unlikely in bronchogenic carcinoma. 0
It has been stated that the diagnosis of a primary lymphoma of the lung requires direct examination to confirm the fact that the lymphoma is predominantly in the lung rather than the mediastinal structures.While direct examination was not possible in the present case since thoracotomy was not done, we believe evidence for primary involvement of the lung was indicated by the fact that at the onset of the illness there was a pneumonic process in the left lower lobe with no evidence of mediastinal or general glandular involvement; nor was there any evidence of subsequent general glandular enlargement. REFERENCES
1 ROSE, A. H.: "Primary Lymphosarcoma of the Lung," ]. Thor. Surg., 33: 254, 1957. 2 BERGHUIS, J., CLAGETT, O. T. AND HARRISON, E. G., JR.: "The Surgical Treatment of Primary Malignant Lymphoma of the Lung,"
Dis. Chest, 40:29, 1961.
3 HALL, E. R., JR. AND BLADES, B.: "Primary Lymphosarcoma of the Lung," Dis. Chest, 36: 571, 1959. 4 SCHUTZ, W. AND KOHN, K.: uDas Primare Retothelsarkom der Lunge," Thoraxchirurgie,
4: 272, 1956. 5 KRESS, M. B. AND BRANTIGAN, O. C.: "Primary Lymphosarcoma of the Lung," Ann. Int. Med., 55:582, 1961. 6 BARON, M. G. AND WHITEHOUSE, W. M.: "Primary Lymphosarcoma of the Lung," Am. ]. Roentgenol., 85: 294, 1961. 7 SAMUELS, M. L., HOWE, C. B., DODD, G. D., JR., FULLER, L. M., SHULLENBERGER, C. C. AND LEARY, W. L.: "Endobronchial Malignant Lymphoma," Am. ]. Roentgenol., 85: 87, 1961.
FATAL CORONARY-ARTERY EMBOLISM AFTER RESECTION A case of thrombosis In a ligated pulmonary vein stump and subsequent fatal coronary artery embollsm after pulmonary resection for bronchogenic carcinoma Is presented. Although this appears to be an unusual complication of pulmonary resection, It Is suggested that further cases may be discovered
by awareness of this diagnostic posslbillty and careful anatomic study at postmortem examination. ). D. AND PEASLEY, E. D.: "Fatal Coronary Artery Embolism after Pulmonary Resection, Ntw Engl. ]. Med., 268:1444, 1963.
SPRINKLE,
Of