Int. .I. Radiation
Oncology Biol. Phys..
1977. Vol. 2, pp. 149-153.
Pergamon
Press.
Printed in the USA
??Brief Communication LYMPHANGITIC PATHOLOGIC, NATHAN
CARCINOMATOSIS DIAGNOSTIC AND CONSIDERATIONS
OF THE LUNG: THERAPEUTIC
M.D.,? WILLIAM KERN, M.D.,S ROBERT LEVIS, M.D., WILLIAM SCHLEITER, M.D.,§ JIM BONORRIS, M.D.7 and GREEN,
CLARENCE J. BERNE, M.D.” Hospitalof the Good Samaritan, Los Angeles, Calif. A review of the tumor registry files of 269 breast cancer patients revealed 24 patients who had lymphangitic carcinomatosis; 17 patients had autopsies. In addition to permeation of the pulmonary lymphatics by tumor, most patients also had pulmonary or pleural nodules, hilar or mediastfnal lymph node metastases or tumor emboli in small arteries and arterioles. In four patients only lymphangitic metastases were observed. The clinical diagnosis usually was made from chest X-ray findings of a dilTuse interstitial pattern. Perfusion lung scan findings of an irregular peripheral perfusion defect were helpful in raising the suspicion of lymphangitic carcinomatosis in patients with normal or atypical chest X-ray findings. Patients who were managed by supportive care had a very short survival. Patients who were managed solely with either (single agent) chemotherapy, endocrine ablation surgery or whole lung irradiation falled to respond to treatment and also had a very short survival. Patients who were managed by whole lung irradiation and combination chemotherapy usually had a favorable response. Dyspnea improved and survival increased. Breast cancer, Lung metastases, Lymphangitic
metastases, Lung lymphangitic
INTRODUCTION
from breast carcinoma, revealed 24 patients who had lymphangitic carcinomatosis. The 24 patients are the source material for this report. A total of 16 patients had a clinical diagnosis of lymphangitic carcinomatosis and 17 patients had autopsies. The age range was from 29 to 84 years. The median age was 56 years. All patients had chest X-rays within 2 months of death. The chest X-ray findings were categorized according to the prominent features: normal, interstitial pattern, parenchymal densities and pleural fluid. A total of 4 patients had ‘9mTechnetium microaggregated perfusion lung scans and three patients had ‘33Xenon ventilation lung scans within 2 months of death. Two had pulmonary function studies while 9 patients had arterial blood oxygen saturation and arterial pO1 determinations. A total of 15 patients received primary
Lymphangitic carcinomatosis is a relatively uncommon disorder characterized by diffuse permeation of the pulmonary lymphatics with metastatic cancer.13 It is a late and distressing manifestion of malignancy that presages early death. The diagnosis can be difficult and often is not made anti mortem.’ The purpose of this report is to review the pathology, diagnositic features and therapeutic response of patients with lymphangitic carcinomatosis from breast cancer. For the past 5 years whenever possible, we have used and combination whole lung irradiation chemotherapy. Treatment was palliative but offered some relief. METHODS
AND
MATERIALS
Between 1967 and 1975, a review of the tumor registry files of 269 patients who died tDivision of *Department ODepartment IDepartment “Department
metastases.
Radiation Therapy. of Pathology, of Radiology. of Medical Oncology. of Surgery.
Reprint requests to: Nathan Green, M.D., Division of Radiation Therapy, Valley Presbyterian Hospital, 15107 Vanowen Street, Van Nuys, CA 91405, U.S.A. 149
150
Radiation Oncology 0 Biology 0 Physics
treatment. The decision to offer treatment and the method of treatment were determined by physician preference. Of the 15, 8 patients were referred for radiotherapy. These patients were managed whenever possible with whole lung irradiation and systemic therapy. However, 2 patients received solely whole lung irradiation. A total of 7 patients were managed solely with systemic therapy. Whole lung irradiation was given with Yo teletherapy, 100 rad per day 5 days per week. The total planned dose was 1400-1700rad. The mediastinum was excluded from the treatment field in order to spare bone marrow. Two patients received a lower total dose because of a declining physical condition. Systemic therapy included single agent chemotherapy, combination chemotherapy and endocrine ablation surgery. Single agents used were adriamyacin 60 mg/m’ i.v. every 3 weeks; cyclophosphamide 10 mg/kg i.v. every week; triethylenethiophosphoramide 0.2 mgl kg i.v. for 5 days and then mainte-
January-February 1977, Volume 2, No. 1 and No. 2
nance. Combination chemotherapy used were S-fluorouracil, cyclophosphamide, vincristine and methotrexate given either in weekly injections or for 5 successive days repeated each month.’ Schedules were individualized to patient tolerance. All patients had dyspnea either at rest or with exertion. The response of dyspnea to treatment was noted. The objective response was evaluated from chest X-rays taken before and after treatment. A complete response would be complete clearing of the radiographic findings for a minimum of 2 months. A partial response would be more than 50 per cent clearing of the radiographic findings for 2 months. Survival was recorded from diagnosis. Autopsy material was reviewed and the findings categorized as extensive lymphangitic involvement meeting the criteria of generalized permeation of pulmonary lymphatics throughout the lung; focal lymphangitic involvement with permeation of some, but not
Table 1. Chest X-ray, lung scan and laboratory findings Clinical diagnosis
Chest X-ray findings
Perfusion lung scan
S.B. Yes Yes J.B. H.C. Yes E.E. Yes M.J. Yes T.J. Yes M.L. Yes A.M. Yes E.M. Yes A.N. Yes L.T. Yes A.G. No R.C. No M.C. Yes R.B. Yes J.M. Yes H.W. Yes J.O. No M.R. No M.T. No R.W. Yes M.M. No C.R. No M.K. No
Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Normal Normal Normal Normal Normal Normal Effusion Effusion Effusion Nodules
t
tBlank
areas = none.
Ventilation lung scan
Pulmonary function studies
Arterial blood PO2
Low Restrictive Low Low
Abnormal
Normal
Abnormal
Normal
Abnormal
Normal
Abnormal
Low Low
Restrictive
Low Low Low Low
Lymphangitic carcitiomatosis of the lung ON.
all pulmonary lymphatics, or associated pulmonary nodules that could be considered to be an equal or more important finding.‘+’ RESULTS Diagnostic
features
A total of 5 patients had pulmonary metastases or malignant pleural effusions present 8-44 months prior to the onset of lymphangitic carcinomatosis. These findings cleared with systemic therapy. The onset of lymphangitic carcinomatosis was associated with new and different chest X-ray findings. Of interest were 6 patients with a normal chest X-ray. Four patients had *“Technetium microaggregated perfusion lung scans. A pattern of multiple irregular peripheral perfusion defects was observed. The 133Xenon ventilation lung scans were normal. Of these patients, 3 had autopsy findings of tumor emboli in small arteries and arterioles. A total of 9 patients had arterial blood oxygen saturation determinations with values that ranged from 74 to 83 per cent. The p0, values ranged from 37 mm Hg to 65 mm Hg. Normal p0, values were 75 mm Hg 25. In two patients who had pulmonary function studies, a restrictive pattern was shown. The vital capacity and total lung capacity were decreased (Table 1). Treatment
response
A total of 5 patients had a favorable response to treatment; 4 patients had partial clearing of an interstitial pattern, and 1 had complete resolution of the pleural fluid. Dyspnea improved in all 5 patients, but recurred in 3 prior to death. Of the 4 patients who were treated with whole lung irradiation and combination chemotherapy, three had a favorable partial response. Patient J.B. was managed by whole lung irradiation and bilateral oophorectomy. She had a favorable partial pulmonary response but continued to develop progressive bone, soft tissue and visceral metastasis. The response to each treatment modality used was assessed. A favorable response was observed in 44 patients who received combination chemotherapy and 44 patients who received whole lung irradiation. No response was observed in patients treated solely with
GREENet al.
151
either whole lung irradiation, single agent chemotherapy or endocrine ablation surgery. Survival was longest in patients who had a favorable treatment response. The median duration of survival was 7 months for responders, 1 month for non responders and 1 month for patients who did not receive specific treatment. (Table 2). Autopsy findings
Of 269 registered breast cancer patients, 42 patients had autopsies. Seventeen patients showed lymphangitic pulmonary spread and are included in this study group. In 11 patients, the lymphangitic involvement was extensive. Five patients had focal lymphangitic involvement and one patient had pulmonary nodules with adjacent lymphatic permeation (Table 3). Sub pleural and pulmonary nodules, hilar and mediastinal nodal metastases and tumor emboli in small arteries and arterioles were present in 13 patients. Four patients had no associated findings, there being only permeation of pulmonary lymphatics by tumor. DISCUSSION Lymphatic spread in the lung is common in breast cancer. The mere presence of lymphatic spread in association with extensive metastatic disease of the conventional pattern should not lead to the classification of “lymphangitic carcinomatosis” a fairly characteristic pathologic finding of extensive and generalized permeation of pulmonary lymphatics by metastatic cancer.‘.13 Lymphangitic carcinomatosis has been observed as a terminal event in up to 25 per cent of patients with breast cancer.4 Of our patients, 8 per cent had an anti mortem diagnosis of lymphangitic carcinomatosis; 40 per cent of the autopsied patients were found to have lymphangitic metastases. The pathogenesis of lymphangitic carcinomatosis is unknown. A few of our patients had pulmonary metastases or malignant pleural effusion which were treated successfully prior to the onset of lymphangitic carcinomatosis. The development of lymphangitic carcinomatosis was a separate event. Mueller and Sniffen believed there is retrograde permeation of pulmonary lymphatics
152
Radiation
Oncology
0 Biology
0 Physics
January-February
197,
Volume
2, No.
1 and No. 2
Table 2. Response to treatment
Patient
Endocrine ablative surgery
J.B. E.E.
Bilateral oophorectomy t
T.J. L.T. C.R. H. C.
Bilateral adrenalectomy Bilateral adrenalectomy
Chemotherapy
Cyt, Vincristine Mtx, S-FuS Cyt, Vincristine Mtx, S-Fu Cyt, Vincristine Mtx, S-Fu Cyt, Vincristine Mtx, .5-Fu
S.B. H. W. M.J.
Adriamycin
M.L. A.N.
Cyt.
Whole lung irradiation (rad)
Treatment response
1400
Yes
7
1700
Yes
7
1300
Yes
3
1650
Yes
7
Yes
13
600 1200 1500
Bilateral oophorectomy
E.M.
Prednisone triethylene thiophosphoramide Adriamycin Cyt, Vincristine Mtx, 5-Fu Cyt, Vincristine Mtx, 5-Fu Adriamycin
J.M. A.M. M. C.
tBlank space = none. SCyt. = cytoxan; Mtx. = methotrexate;
1400
Survival (months)
No No No
No No No
1
No
2
No
2
No
1
No
2
S-Fu = S-Fluorouracil.
Table 3. Autopsy findings
Lymphangitic carcinomatosis Extensive (11) Focal (5) Associated with nodules (1)
Pulmonary nodules less than 1.5 cm
Pleural nodules less than 0.5 cm
Hilar mediastinal nodal metastases
Arterial tumor emboli
3/11 215
s/11 015
4/11 3/s
3/11 115
2/11 215
l/l
O/l
O/l
O/l
O/l
from positive hilar nodes.9 Others suggested the primary pathogenesis is vascular embolization with subsequent tumor invasion through blood vessel walls into adjacent Most of our patients had associated pathologic findings of mediastinal or hilar nodal metastases, parenchymal or sub pleural nodules, or tumor emboli in small lymphatiCs.6,7.‘4.‘5,16
No associated findings
arteries and arterioles. However, in 4 patients, only lymphangitic metastases were observed. The diagnosis of lymphangitic carcinomatosis can be suspected from the chest X-ray findings of a diffuse interstitial pattern.3,9.‘4 Most patients are hypoxic. Pulmonary function studies show a restrictive pattern.’ The diagnosis may be especially
Lymphangitic carcinomatosis of the lung 0 N. GREENet al. difficult if the chest X-rays are normal or show atypical findings. In these patients, the perfusion lung scan findings of multiple irregular peripheral perfusion defects may be helpful. The perfusion defects are caused by tumor emboli in small arteries and arterioles.5~“~‘2 The life expectancy of patients with lymphangitic carcinomatosis has been short.“.” In our experience, patients who were managed solely by supportive care had a median survival of 1 month. Patients who failed to respond to the initial therapeutic regimens also did not survive long. Alternate therapeutic trials rarely could be employed as death was imminent. Single agent chemotherapy and endocrine ablation surgery were not of value. Combination chemotherapy has been reported to induce remission and prolong life. (Sadoff, L., Grossman, J., Werner, M.: Oral communication, July 1975). Whole lung irradi-
153
ation also may induce a remission. One of our patients who was treated by whole lung irradiation and bilateral oophorectomy had a favorable pulmonary response while developing progressive bone, soft tissue and visceral metastasis. In patients with a very short life expectancy, it is reasonable to use concurrently all modalities that offer prospects for remission. In our experience, the concurrent use of combination chemotherapy and whole lung irradiation was worthwhile. Treatment response usually was favorable. Dyspnea was alleviated. Survival was increased. The treatment regimen was well tolerated. Prior horagent manipulation and single monal chemotherapy did not appear to adversely affect the ability to deliver effective combination chemotherapy and radiotherapy.” Unfortunately, the improvement in symptoms and survival was of relatively short duration.
REFERENCES 1. Alkalay, J., Fairfax, C.W., Bullard, J.C.: 10. Otis, P.T., Armentraut, S.A.: Combination Lymphangitic carcinomatosis of the lungs with chemotherapy in metastatic carcinoma of the normal appearing chest X-ray films. Chest 62: breast-results in a three drug combination. 228-230, Aug. 1972. Cancer 36(2): 311-317, 1975. 2. Carter, S.K.: Single and combination non 11. Pendergrass, H.P., Nelly, H.J., Clement, P.B., hormonal chemotherapy in breast cancer. pattern asPostoid, N.J.: Lung perfusion sociated with widespread occlusion of the Cancer 30(6): 1543-1556, Dec. 1972. 3. Chandler, G.M.: Lymphangitis carcinomatosa. pulmonary vessels and lymphatics. Radiology Br. Med. J. 2: 639-641, Sept. 1952. 105: 615-616, Dec. 1972. 4. Goldsmith, H.S., Bailey, H.D., Callahan, E.L., 12. Poe, M.D., Taplin, G.V.: Pulmonary Scanning Beattie, E.J.: Pulmonary lymphangitic metasin Nuclear Medicine, 2nd Edn. ed. by Blahd, tases from breast carcinoma. Arch. Surg. 94: W.H. New York, McGraw-Hill, 1972, pp. 483-494, Apr. 1967. 313-350. 5. Green, N., Swanson, L., Kern, W., Homann, 13. Spender, H.: Pathology of the Lung, 2nd Edn, R., Irwin, L., Berne, C.J.: Lymphangitic carOxford, Pergamon Press, 1968, pp. 993-1005. cinomatosis: lung scan abnormalities. J. Nucl. 14. Trapnell, D.H.: Radiological appearances of Med. 17: 258-260, Apr. 1976. lymphangitic carcinomatosa of the lung. 6. Harold, J.T.: Lymphangitic carcinomatosa of Thorax 19: 251-260, 1964. the lungs. Q. J. Med. 83: 353-360, Oct. 1956. 15. Trapnell, D.H.: The peripheral lymphatics of 7. Janower, M.L., Blennerhassett, J.B.: Lymthe lung. Br. J. Radiol. 36(429): 660-672, 1963. 16. White, W.F., Urquhart, W.: The demonstration phangitic spread of metastatic cancer to the lung. Radiology 101: 267-273, Nov. 1971. of pulmonary lymphatics by lymphography in a 8. Motley, H.: Pulmonary function studies in patient with chylothorax. Clin. Radiol. 17: chronic restrictive lung disease without em92-94, 1966. 17. Wu, T.T.: Generalized lymphatic carcinosis physema: right to left shunting the major factor for hypoxia. Med. Thorac. 21: 65-67, 1964. (“Lymphangitic Carcinomatosa”) of the lungs. 9. Mueller, H.P., Sniffen, R.C.: Roentgenologic J. Path. Bateriol. 43: 61-76, 1936. appearance and pathology of intrapulmonary 18. Yang, Sze-piao, Che-Chung, Lin: Lymphangilymphatic spread of metastatic cancer. Am. J. tic carcinomatosis of the lungs. Chest 62(2): Roentgenol. 53(2): 109-123, Feb. 1945. 179-187, Aug. 1972.
Oncology Biol. Phys..
1977. Vol. 2, pp. 149-153.
Pergamon
Press.
Printed in the USA
??Brief Communication LYMPHANGITIC PATHOLOGIC, NATHAN
CARCINOMATOSIS DIAGNOSTIC AND CONSIDERATIONS
OF THE LUNG: THERAPEUTIC
M.D.,? WILLIAM KERN, M.D.,S ROBERT LEVIS, M.D., WILLIAM SCHLEITER, M.D.,§ JIM BONORRIS, M.D.7 and GREEN,
CLARENCE J. BERNE, M.D.” Hospitalof the Good Samaritan, Los Angeles, Calif. A review of the tumor registry files of 269 breast cancer patients revealed 24 patients who had lymphangitic carcinomatosis; 17 patients had autopsies. In addition to permeation of the pulmonary lymphatics by tumor, most patients also had pulmonary or pleural nodules, hilar or mediastfnal lymph node metastases or tumor emboli in small arteries and arterioles. In four patients only lymphangitic metastases were observed. The clinical diagnosis usually was made from chest X-ray findings of a dilTuse interstitial pattern. Perfusion lung scan findings of an irregular peripheral perfusion defect were helpful in raising the suspicion of lymphangitic carcinomatosis in patients with normal or atypical chest X-ray findings. Patients who were managed by supportive care had a very short survival. Patients who were managed solely with either (single agent) chemotherapy, endocrine ablation surgery or whole lung irradiation falled to respond to treatment and also had a very short survival. Patients who were managed by whole lung irradiation and combination chemotherapy usually had a favorable response. Dyspnea improved and survival increased. Breast cancer, Lung metastases, Lymphangitic
metastases, Lung lymphangitic
INTRODUCTION
from breast carcinoma, revealed 24 patients who had lymphangitic carcinomatosis. The 24 patients are the source material for this report. A total of 16 patients had a clinical diagnosis of lymphangitic carcinomatosis and 17 patients had autopsies. The age range was from 29 to 84 years. The median age was 56 years. All patients had chest X-rays within 2 months of death. The chest X-ray findings were categorized according to the prominent features: normal, interstitial pattern, parenchymal densities and pleural fluid. A total of 4 patients had ‘9mTechnetium microaggregated perfusion lung scans and three patients had ‘33Xenon ventilation lung scans within 2 months of death. Two had pulmonary function studies while 9 patients had arterial blood oxygen saturation and arterial pO1 determinations. A total of 15 patients received primary
Lymphangitic carcinomatosis is a relatively uncommon disorder characterized by diffuse permeation of the pulmonary lymphatics with metastatic cancer.13 It is a late and distressing manifestion of malignancy that presages early death. The diagnosis can be difficult and often is not made anti mortem.’ The purpose of this report is to review the pathology, diagnositic features and therapeutic response of patients with lymphangitic carcinomatosis from breast cancer. For the past 5 years whenever possible, we have used and combination whole lung irradiation chemotherapy. Treatment was palliative but offered some relief. METHODS
AND
MATERIALS
Between 1967 and 1975, a review of the tumor registry files of 269 patients who died tDivision of *Department ODepartment IDepartment “Department
metastases.
Radiation Therapy. of Pathology, of Radiology. of Medical Oncology. of Surgery.
Reprint requests to: Nathan Green, M.D., Division of Radiation Therapy, Valley Presbyterian Hospital, 15107 Vanowen Street, Van Nuys, CA 91405, U.S.A. 149
150
Radiation Oncology 0 Biology 0 Physics
treatment. The decision to offer treatment and the method of treatment were determined by physician preference. Of the 15, 8 patients were referred for radiotherapy. These patients were managed whenever possible with whole lung irradiation and systemic therapy. However, 2 patients received solely whole lung irradiation. A total of 7 patients were managed solely with systemic therapy. Whole lung irradiation was given with Yo teletherapy, 100 rad per day 5 days per week. The total planned dose was 1400-1700rad. The mediastinum was excluded from the treatment field in order to spare bone marrow. Two patients received a lower total dose because of a declining physical condition. Systemic therapy included single agent chemotherapy, combination chemotherapy and endocrine ablation surgery. Single agents used were adriamyacin 60 mg/m’ i.v. every 3 weeks; cyclophosphamide 10 mg/kg i.v. every week; triethylenethiophosphoramide 0.2 mgl kg i.v. for 5 days and then mainte-
January-February 1977, Volume 2, No. 1 and No. 2
nance. Combination chemotherapy used were S-fluorouracil, cyclophosphamide, vincristine and methotrexate given either in weekly injections or for 5 successive days repeated each month.’ Schedules were individualized to patient tolerance. All patients had dyspnea either at rest or with exertion. The response of dyspnea to treatment was noted. The objective response was evaluated from chest X-rays taken before and after treatment. A complete response would be complete clearing of the radiographic findings for a minimum of 2 months. A partial response would be more than 50 per cent clearing of the radiographic findings for 2 months. Survival was recorded from diagnosis. Autopsy material was reviewed and the findings categorized as extensive lymphangitic involvement meeting the criteria of generalized permeation of pulmonary lymphatics throughout the lung; focal lymphangitic involvement with permeation of some, but not
Table 1. Chest X-ray, lung scan and laboratory findings Clinical diagnosis
Chest X-ray findings
Perfusion lung scan
S.B. Yes Yes J.B. H.C. Yes E.E. Yes M.J. Yes T.J. Yes M.L. Yes A.M. Yes E.M. Yes A.N. Yes L.T. Yes A.G. No R.C. No M.C. Yes R.B. Yes J.M. Yes H.W. Yes J.O. No M.R. No M.T. No R.W. Yes M.M. No C.R. No M.K. No
Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Interstitial Normal Normal Normal Normal Normal Normal Effusion Effusion Effusion Nodules
t
tBlank
areas = none.
Ventilation lung scan
Pulmonary function studies
Arterial blood PO2
Low Restrictive Low Low
Abnormal
Normal
Abnormal
Normal
Abnormal
Normal
Abnormal
Low Low
Restrictive
Low Low Low Low
Lymphangitic carcitiomatosis of the lung ON.
all pulmonary lymphatics, or associated pulmonary nodules that could be considered to be an equal or more important finding.‘+’ RESULTS Diagnostic
features
A total of 5 patients had pulmonary metastases or malignant pleural effusions present 8-44 months prior to the onset of lymphangitic carcinomatosis. These findings cleared with systemic therapy. The onset of lymphangitic carcinomatosis was associated with new and different chest X-ray findings. Of interest were 6 patients with a normal chest X-ray. Four patients had *“Technetium microaggregated perfusion lung scans. A pattern of multiple irregular peripheral perfusion defects was observed. The 133Xenon ventilation lung scans were normal. Of these patients, 3 had autopsy findings of tumor emboli in small arteries and arterioles. A total of 9 patients had arterial blood oxygen saturation determinations with values that ranged from 74 to 83 per cent. The p0, values ranged from 37 mm Hg to 65 mm Hg. Normal p0, values were 75 mm Hg 25. In two patients who had pulmonary function studies, a restrictive pattern was shown. The vital capacity and total lung capacity were decreased (Table 1). Treatment
response
A total of 5 patients had a favorable response to treatment; 4 patients had partial clearing of an interstitial pattern, and 1 had complete resolution of the pleural fluid. Dyspnea improved in all 5 patients, but recurred in 3 prior to death. Of the 4 patients who were treated with whole lung irradiation and combination chemotherapy, three had a favorable partial response. Patient J.B. was managed by whole lung irradiation and bilateral oophorectomy. She had a favorable partial pulmonary response but continued to develop progressive bone, soft tissue and visceral metastasis. The response to each treatment modality used was assessed. A favorable response was observed in 44 patients who received combination chemotherapy and 44 patients who received whole lung irradiation. No response was observed in patients treated solely with
GREENet al.
151
either whole lung irradiation, single agent chemotherapy or endocrine ablation surgery. Survival was longest in patients who had a favorable treatment response. The median duration of survival was 7 months for responders, 1 month for non responders and 1 month for patients who did not receive specific treatment. (Table 2). Autopsy findings
Of 269 registered breast cancer patients, 42 patients had autopsies. Seventeen patients showed lymphangitic pulmonary spread and are included in this study group. In 11 patients, the lymphangitic involvement was extensive. Five patients had focal lymphangitic involvement and one patient had pulmonary nodules with adjacent lymphatic permeation (Table 3). Sub pleural and pulmonary nodules, hilar and mediastinal nodal metastases and tumor emboli in small arteries and arterioles were present in 13 patients. Four patients had no associated findings, there being only permeation of pulmonary lymphatics by tumor. DISCUSSION Lymphatic spread in the lung is common in breast cancer. The mere presence of lymphatic spread in association with extensive metastatic disease of the conventional pattern should not lead to the classification of “lymphangitic carcinomatosis” a fairly characteristic pathologic finding of extensive and generalized permeation of pulmonary lymphatics by metastatic cancer.‘.13 Lymphangitic carcinomatosis has been observed as a terminal event in up to 25 per cent of patients with breast cancer.4 Of our patients, 8 per cent had an anti mortem diagnosis of lymphangitic carcinomatosis; 40 per cent of the autopsied patients were found to have lymphangitic metastases. The pathogenesis of lymphangitic carcinomatosis is unknown. A few of our patients had pulmonary metastases or malignant pleural effusion which were treated successfully prior to the onset of lymphangitic carcinomatosis. The development of lymphangitic carcinomatosis was a separate event. Mueller and Sniffen believed there is retrograde permeation of pulmonary lymphatics
152
Radiation
Oncology
0 Biology
0 Physics
January-February
197,
Volume
2, No.
1 and No. 2
Table 2. Response to treatment
Patient
Endocrine ablative surgery
J.B. E.E.
Bilateral oophorectomy t
T.J. L.T. C.R. H. C.
Bilateral adrenalectomy Bilateral adrenalectomy
Chemotherapy
Cyt, Vincristine Mtx, S-FuS Cyt, Vincristine Mtx, S-Fu Cyt, Vincristine Mtx, S-Fu Cyt, Vincristine Mtx, .5-Fu
S.B. H. W. M.J.
Adriamycin
M.L. A.N.
Cyt.
Whole lung irradiation (rad)
Treatment response
1400
Yes
7
1700
Yes
7
1300
Yes
3
1650
Yes
7
Yes
13
600 1200 1500
Bilateral oophorectomy
E.M.
Prednisone triethylene thiophosphoramide Adriamycin Cyt, Vincristine Mtx, 5-Fu Cyt, Vincristine Mtx, 5-Fu Adriamycin
J.M. A.M. M. C.
tBlank space = none. SCyt. = cytoxan; Mtx. = methotrexate;
1400
Survival (months)
No No No
No No No
1
No
2
No
2
No
1
No
2
S-Fu = S-Fluorouracil.
Table 3. Autopsy findings
Lymphangitic carcinomatosis Extensive (11) Focal (5) Associated with nodules (1)
Pulmonary nodules less than 1.5 cm
Pleural nodules less than 0.5 cm
Hilar mediastinal nodal metastases
Arterial tumor emboli
3/11 215
s/11 015
4/11 3/s
3/11 115
2/11 215
l/l
O/l
O/l
O/l
O/l
from positive hilar nodes.9 Others suggested the primary pathogenesis is vascular embolization with subsequent tumor invasion through blood vessel walls into adjacent Most of our patients had associated pathologic findings of mediastinal or hilar nodal metastases, parenchymal or sub pleural nodules, or tumor emboli in small lymphatiCs.6,7.‘4.‘5,16
No associated findings
arteries and arterioles. However, in 4 patients, only lymphangitic metastases were observed. The diagnosis of lymphangitic carcinomatosis can be suspected from the chest X-ray findings of a diffuse interstitial pattern.3,9.‘4 Most patients are hypoxic. Pulmonary function studies show a restrictive pattern.’ The diagnosis may be especially
Lymphangitic carcinomatosis of the lung 0 N. GREENet al. difficult if the chest X-rays are normal or show atypical findings. In these patients, the perfusion lung scan findings of multiple irregular peripheral perfusion defects may be helpful. The perfusion defects are caused by tumor emboli in small arteries and arterioles.5~“~‘2 The life expectancy of patients with lymphangitic carcinomatosis has been short.“.” In our experience, patients who were managed solely by supportive care had a median survival of 1 month. Patients who failed to respond to the initial therapeutic regimens also did not survive long. Alternate therapeutic trials rarely could be employed as death was imminent. Single agent chemotherapy and endocrine ablation surgery were not of value. Combination chemotherapy has been reported to induce remission and prolong life. (Sadoff, L., Grossman, J., Werner, M.: Oral communication, July 1975). Whole lung irradi-
153
ation also may induce a remission. One of our patients who was treated by whole lung irradiation and bilateral oophorectomy had a favorable pulmonary response while developing progressive bone, soft tissue and visceral metastasis. In patients with a very short life expectancy, it is reasonable to use concurrently all modalities that offer prospects for remission. In our experience, the concurrent use of combination chemotherapy and whole lung irradiation was worthwhile. Treatment response usually was favorable. Dyspnea was alleviated. Survival was increased. The treatment regimen was well tolerated. Prior horagent manipulation and single monal chemotherapy did not appear to adversely affect the ability to deliver effective combination chemotherapy and radiotherapy.” Unfortunately, the improvement in symptoms and survival was of relatively short duration.
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