Lung (1990) Suppl:1035-1040
N e w York Inc. 1990
Bronchoalveolar Lavage in the Diagnosis of Cancer Stephen I. Rennard Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
Abstract. Bronchoalveolar lavage (BAL) is a widely used clinical procedure. To determine if BAL could provide useful information in the detection of cancer, 850 lavages from 421 patients having BAL for a variety of indications, 50 lavages in patients with Hodgkin's disease and 20 patients with breast cancer undergoing bone marrow transplant were reviewed. BALs were performed with 5 successive 20 cc aliquots in a wedged position. The return from the first aliquot was processed separately from the subsequent four aliquots. Diff-Quik stained cytocentrifuge preparations and Papanicolaou stained millipore filter preparations were analyzed. Thirty-five patients had biopsy-proven lung cancer. In 24 (68.6%) of these, BAL revealed cells diagnostic of malignancy. There were no false positives. Six out of 50 Hodgkin's disease patients had Reed Sternberg ceils detected on BAL, and 7/20 breast cancer patients had malignant cells on BAL prior to chemotherapy. In summary, the routine performance of BAL, an easily performed and well-tolerated procedure, may prove to be useful in the routine assessment of patients for cancer.
Key words: Bronchoalveolar lavage--Cancer--Diagnostic yield--Tumor markers.
This work was co-authored by the members of BAL task group working for lung cancer: C. Albera, R. Cordeiro, W. Bauer, H. Eckert, J. Linder, M. Pirozynski, S. 1. Rennard, C. Sanguinetti, G. Semenzato, I. Striz, H. Teschler, and G. Velluti; with contributions from W. Bauer, L. Bjermer, R. Cordeiro, U. Costabel, C. Danel, C. F. Conner, P. Godard, T. W. Higenbottam, D. Israel-Biet, J. Linder, F. X. Marchandise, M. P. Pirozynski, R. J. Pisani, L. W. Poulter, C. M. Sanguinetti, G. Semenzato, Y. Sibille, I. Striz, G. Velluti, and A. Venet. Offprint requests to: Dr. S. I. Rennard, Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, 600 So. 42nd St, Omaha, NE 68198-2465, USA.
1036
S. I. Rermard Table 1. Examples of BAL used in diagnosis of cancer
Type of Cancer Primary lung Squamous Adenocarcinoma Large cell Small cell Bronchoalveolar Metastatic Solid tumors Breast Lymphangitic spread Hematologic malignancy Hodgkin's Non-Hodgkin's lymphoma Leukemia Waldenstrom's Myeloma Mycosis fungoides
Reference
7, 10, 21, 11 7, 10, 21, 11 7, 10, 21 7, 10, 21 8, 9 7 27 13 20, 23 14, 24, 25 7, 26 15 19 17
The flexible fiberoptic bronchoscope was first introduced by Ikeda to aid in diagnosis of lung cancer [1]. The major diagnostic technique to obtain material for the diagnosis of cancer was, and remains, transbronchoscopic biopsy. Nevertheless, bronchoalveolar lavage (BAL) can obtain material which permits the cytologic diagnosis of cancer. The criteria for the cytologic diagnosis of cancer in the lung are well established [2-4]. However, since BAL is often performed and interpreted by pulmonologists [5-7] who are not trained cytologists and because the stains most often used by pulmonologists do not always reveal cytologic detail, it is likely that the power of BAL to aid in the diagnosis of lung cancer has gone underappreciated. Recent studies indicate that bronchoalveolar lavage can aid in the diagnosis of cancer. The exact circumstances in which lavage will be most important and the diagnostic yield comparable to other techniques are, as yet, unanswered questions. Nevertheless, because of the ease of performance of the procedure and its relative safety, BAL must be considered one of the tools available to the clinician who must obtain material for the diagnosis of malignancy in the lung. In addition, it should be recognized that BAL performed for other reasons may reveal malignant cells in cases where cancer is not suspected. A rapidly enlarging collection of case reports and small series suggest that BAL can be of use in the diagnosis of a number of malignancies in the lung (Table 1). With regard to primary lung cancers, there are six series (including unpublished data contributed by the co-authors of this document) which address the issue of diagnostic yield of BAL (Table 2). Overall, the diagnostic yield was about 50% in these five series ranging from 35% to 69%. Only two of the centers categorized cases based on cell type. While the numbers are small,
BAL in the Diagnosis of Cancer
1037
Table 2. Diagnostic yield of bronchoalveolar lavage in lung cancer Contributor
No. of cases
No. with both BAL and diagnosis of cancer
No. of cases positive by BAL
Striz Worth Baglin et al. [12] Pirozynski Linder Schaberg et al. [38] Total
471 146 46 124 421 31
430 225 99 37 21 13 124 44 35 24 21 3 730 346 For sites, mean = 45 For cases, mean = 47
Percentage of cases positive by BAL 52 37 62 35 69 14
Table 3. Diagnostic yield for BAL in lung cancer Cell type* Bronchoalveolar cell carcinoma Small cell Squamous Adeno Large cell
Percentage yield (%) 11/12 10/35 2/3 9/49 7/10 11/20 12/15 0/5 3/7
92 32 27 66 25
* Data is reported for the various series available expressed as no. cases positive by BAL/no. cases of proven cancer undergoing BAL
the available data suggests that the diagnostic yield of BAL might be higher for bronchoalveolar cell carcinoma than for other cell types of primary pulmonary malignancy (Table 3). There are several important unanswered questions in these series, so it is not currently possible to compare lavage with other diagnostic techniques for malignancies in various distributions. It would be ideal to compare lavage with transbronchial biopsy, for example, for peripheral lesions, diffuse lesions and large central bronchoscopically visible lesions. Studies designed to address these issues are currently underway. While it is not possible to draw any firm conclusions, lavage can be of use in some cases of isolated peripheral nodules. It was also felt that lavage was particularly useful in diffuse lesions, such as those found with bronchoalveolar cell carcinoma. Thus, while lavage can clearly provide diagnostic material in a variety of clinical settings, its yield in specific settings remains to be determined. A second limitation of lavage is that the cytologic diagnosis of malignancy does not always correspond to the
1038
S . I . Rennard
histologic pattern [11]. Thus, in the series of Linder, cytology agreed with biopsy in only 80% of cases. The major difficulty was in distinguishing large cell undifferentiated carcinoma from adenocarcinoma. A similar problem occurs with the severe dysplastic changes that can develop in airway epithelial cells in a variety of clinical circumstances including pneumonia, viral infections and that following chemotherapy. These severe dysplastic changes can be very difficult to distinguish from malignant changes. These limitations of cytologic methods must be considered when bronchoalveolar lavage is used in the diagnosis of lung cancer. Several contributors to the current report have performed large series of BALs and have made a diagnosis of malignancy only very rarely. This has contributed to the impression that BAL has limited use in the diagnosis of cancer. There are several reasons which may explain the low diagnostic yield at these centers: 1) case selection may have been very different at different centers; 2) pulmonologists interested in performing BAL for specific research goals may not have processed lavage specimens in a manner to maximize yield for malignancy. Some investigators, for example, throw away the first aliquot returned, which is relatively enriched for bronchial material; for malignancies originating in the bronchial tree, this may represent the material with the highest diagnostic yield. In addition, many investigators filter the fluid through loose-weave gauze in order to remove mucus. Malignant cells are often present as clumps and may be removed by such filtration procedures. Finally, many investigators have performed the procedure in patients with malignancy in order to investigate immunologic abnormalities in these patients. They have intentionally lavaged sites not affected by the cancer. Thus, the relatively low diagnostic yield found by many investigators who have performed !avage for reasons other than to obtain diagnostic material, may reflect the interests of specific investigators rather than the utility of lavage to obtain material diagnostic of malignancy. A number of tumor markers have been studied in BAL [21, 28-35]. While there is considerable interest among investigators in such markers, none has proved to be diagnostic. Thus, the use of these markers must be considered a research tool at present. Whether these markers will be helpful in following patients on therapeutic protocoIs for malignancy is an interesting, but as yet unresolved, question. One investigator has suggested that cytologic assessment of malignancy can be used for a similar purpose. Again, this must be considered a research undertaking. However, inasmuch as BAL might provide a means to assess efficacy of novel therapeutic strategies in lung cancer, it may become an important adjunct in clinical studies. There is also a considerable interest in studying abnormalities in the patient with cancer. As such, a number of studies of bronchoalveolar lavage parameters have been undertaken in these patients [for reviews, please see Refs. 36, 37]. While these studies promise to provide some information as to why certain individuals develop malignancy and, perhaps, why these patients have increased incidences of lower respiratory tract infections, they are in fact research studies.
BAL in the Diagnosis of Cancer
1039
It is difficult to summarize current consensus regarding the use of bronchoalveolar lavage for the diagnosis of lung cancer. Current practices vary from never performing this procedure for this indication to routine performance. At institutions where this procedure is never performed, there is, obviously, no diagnostic yield associated with BAL. Centers where bronchoalveolar lavage has been found to be useful in the diagnosis of lung cancer are those centers where the procedure can be performed readily, the samples can be processed easily and trained personnel are available for the routine analysis of the specimens. In such a favorable setting, it would seem reasonable to include bronchoalveolar lavage in the diagnostic armamentarium used to evaluate patients for lung cancer. This is particularly so considering that the procedure has exceedingly low morbidity, and the increased cost over performing a bronchoscopy with other diagnostic procedures is relatively low.
References 1. Ikeda S (1974) Atlas of flexible bronchofiberscopy. City: University of Park Press, p 000 2. Johnston WW, Bossen EH (1981) Ten years of respiratory cytopathology at Duke University Medical Center: I. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, noting the significance of specimen number and type. Acta Cytol 25:103-107 3. Johnston WW, Bossen EH (1981) Ten years of respiratory cytopathology at Duke University Medical Center: II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer. Acta Cytol 25:499-505 4. Johnson WW, Frable WJ (1976) The cytopathology of the respiratory tract: a review. Am J Pathol 84:372-424 5- Reynolds HY (1987) State of the art: bronchoalveolar lavage. Am Rev Respir Dis 135:250-263 6. Reynolds HY, Chretian J (1984) Respiratory tract fluids: analysis of content and contemporary use of understanding lung diseases. DM 30:1-103 7. Linder J, Rennard S (1988) Bronchoalveolar Lavage. Chicago: ASCP Press, pp 1-196 8. Springmeyer SC Hackman R, Carlson JJ, McClellan JE (1983) Bronchiolo-alveolar cell carcinoma diagnosed by bronchoalveolar lavage. Chest 83:278-279 9. Sestini P, Rottoli L, Gotti G, Miracco C, Luzi P (1985) Bronchoalveolar lavage diagnosis of bronchiolo-alveolar carcinoma. Eur J Respir Dis 66:55-58 10. Korfhage L, Broghamer, WL, Richardson ME, Parker JE, Gilkey CM (1986) Pulmonary cytology in the posttherapeutic monitoring of patients with bronchogenic carcinoma. Acta Cytol 30:351-355 11. Linder J, Radio SJ, Robbins RA, Ghafouri M, Rennard SI (1987) Bronchoalveolar lavage in the cytologic diagnosis of carcinoma of the lung. Acta Cytol 31:796-801 12. Baglin JY, Danel C, Carnot F, Lacronique J, Jaubert F, Chretien J (1984) Interest of bronchoalveolar lavage (BAL) in the diagnosis of lung tumors with normal fiberoptic examination. Proceedings International Conference on Bronchoalveolar Lavage, Columbia, Maryland 13. FeduUo A J, Ettensohn DB (1985) Bronchoalveolar lavage in lymphangitic spread of adenocarcinoma to the lung. Chest 87:129-131 14. Davis WB, Gadek JE (1987) Detection of pulmonary lymphoma by bronchoalveolar lavage. Chest 91:787-790 t5. Kobayashi H, Ii K, Hizawa K, Maeda T (t985) Two cases of pulmonary Watdenstrom's macroglobulinemia. Chest 88:297-299 16. Levy H, Horak DA, Lewis MI (1988) The value of bronchial washings and bronchoalveolar lavage in the diagnosis of lymphangitic carcinomatosis. Chest 94:1028-1030
1040
S.I. Rennard
17. Miller KS, Sahn SA (1986) Mycosis fungoides presenting as ARDS and diagnosed by bronchoalveolar lavage. Chest 89:312-314 18. Myers JL, Fulmer JD (1987) Bronchoalveolar lavage in the diagnosis of pulmonary lymphomas. Chest 91:642-643 19. Weynants P, Cordier JF, Cellier CC, Pages J, Loire R, Brune J (1985) Primary immunocytoma of the lung: the diagnostic value of bronchoalveolar lavage. Thorax 40:542-543 20. Morales FM, Matthews JI (1987) Diagnosis of parenchymal Hodgkin's disease using bronchoalveolar lavage. Chest 91:785-787 21. Wiesner B, Knoll P, Jager J, Kessler G (1986) Value ofbronchoalveolar lavage for the diagnosis of adenocarcinoma of the lung. Z Erkr Atmungsorgane 167(1/2):158-162 22. Ghafouri MA, Rasmussen JK, Sears K, Clayton M, Ertl RF, Robbins R.A, Rermard SI (1985) Use of sequential bronchoalveolar lavage to enrich for "bronchial" and "alveolar" material. Clin Res 33:464A 23. Wisecarver J, Ness MJ, Rennard SI, Armitage JO, Linder J (1989) Bronchoalveolar lavage in the assessment of pulmonary Hodgkin's disease. Acta Cytol 33:527-532 24. Costabel U, Bross KJ, Matthys H (1985) Diagnosis of bronchoalveolar lavage of cause of pulmonary infiltrates in haematological, malignancies. Brit Med Journal 290:1041 25. Costabel U, Bross KJ, Guzman J, Matthys H (1987) Bronchoalveolar lavage in patients with pulmonary infiltrates caused by malignancies. Atemw-Lungenkrkh, Jahrgang 13:79-82 26. Rossi GA, Baibi B, Risso M, et al (1985) Acute myelomonocytic leukemia: demonstration of pulmonary involvement by bronchoalveolar lavage. Chest 87:259-260 27. Radio SJ, Rennard SI, Kessinger A, Vaughan WP, Linder J (1989) Breast carcinoma in bronchoalveolar lavage. Arch Pathol Lab Med 113:333-336 28. Merrill WW, Barwick KW, Madri J, Strober W, Matthay RA, Olchowski J, Naegel G, Reynolds HY (1984) Bronchial lavage proteins as correlates of histopathologic airway changes in healthy smokers and patients with pulmonary carcinoma. Am Rev Respir Dis 130:905-909 29. Goldstein N, Lippmann ML, Goldberg SK, Fein AM, Shapiro B, Leon SA (1985) Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy. Am Rev Respir Dis 132:60-64 30. Schweisfurth H, Leppert R (1987) Kininase II in bronchoalveolar lavage fluid and serum of patients with pulmonary disorders. Clin Biochem 20:419-422 31. Blair OM, Goldenberg DM (1974) A correlative study of bronchial cytology, bronchial washing carcinoembryonic antigen and plasma carcinoembryonic antigen in the diagnosis of bronchogenic cancer. Acta Cytol 18:510-514 32. Molodyk AA, Krumm AV (1986) Carcinoembryonic antigen in bronchoalveolar lavage fluids in the diagnosis of lung cancer. Med Radiol 31:51-55 33. Macchia V, Mariano A, Cavalcanti M, Coppa A, Cecere C, Fraioli G, Elia S, Ferrante G (1987) Tumor markers and lung cancer: correlation between serum and bronchial secretion levels of CEA, TPA, CANAG CA-50, NSE and ferr/tin. Int J Biol Markers 2:151-156 34. Semeraro N, De Lucia O, Lattanzio A, Montemurro P, Giordano D, Loizzi M, Carpagnano F (1986) Procoagnlant activity of human alveolar macrophages: different expression in patients with lung cancer. Int J Cancer 37:525-529 35. Robalo-Corde/ro AJA, Rosa MS, Moreira MS, Loureiro MC, Leite ACP, De Almeida JRG, Gaspar E, Garcao MF (1987) Carcinoma Bronquico. Coimbra Med 8:121-132 36. Olsen GN, Gangemi JD (1985) Bronchoalveolar lavage and the immunology of primary lung cancer. Chest 87:677-683 37. Semenzato G (submitted) The role of bronchoalveolar lavage in providing access to the evaluation of immune mechanisms taking place in lung cancer. 38. Schaberg T, Hennig H, Rahn W, Preussler H, Loddenkemper R (in Press) Stellenwert der bronchoalveol re lavage (BAL) in der diagnostik yon tumorerkrankungen der lunge.
N e w York Inc. 1990
Bronchoalveolar Lavage in the Diagnosis of Cancer Stephen I. Rennard Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
Abstract. Bronchoalveolar lavage (BAL) is a widely used clinical procedure. To determine if BAL could provide useful information in the detection of cancer, 850 lavages from 421 patients having BAL for a variety of indications, 50 lavages in patients with Hodgkin's disease and 20 patients with breast cancer undergoing bone marrow transplant were reviewed. BALs were performed with 5 successive 20 cc aliquots in a wedged position. The return from the first aliquot was processed separately from the subsequent four aliquots. Diff-Quik stained cytocentrifuge preparations and Papanicolaou stained millipore filter preparations were analyzed. Thirty-five patients had biopsy-proven lung cancer. In 24 (68.6%) of these, BAL revealed cells diagnostic of malignancy. There were no false positives. Six out of 50 Hodgkin's disease patients had Reed Sternberg ceils detected on BAL, and 7/20 breast cancer patients had malignant cells on BAL prior to chemotherapy. In summary, the routine performance of BAL, an easily performed and well-tolerated procedure, may prove to be useful in the routine assessment of patients for cancer.
Key words: Bronchoalveolar lavage--Cancer--Diagnostic yield--Tumor markers.
This work was co-authored by the members of BAL task group working for lung cancer: C. Albera, R. Cordeiro, W. Bauer, H. Eckert, J. Linder, M. Pirozynski, S. 1. Rennard, C. Sanguinetti, G. Semenzato, I. Striz, H. Teschler, and G. Velluti; with contributions from W. Bauer, L. Bjermer, R. Cordeiro, U. Costabel, C. Danel, C. F. Conner, P. Godard, T. W. Higenbottam, D. Israel-Biet, J. Linder, F. X. Marchandise, M. P. Pirozynski, R. J. Pisani, L. W. Poulter, C. M. Sanguinetti, G. Semenzato, Y. Sibille, I. Striz, G. Velluti, and A. Venet. Offprint requests to: Dr. S. I. Rennard, Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, 600 So. 42nd St, Omaha, NE 68198-2465, USA.
1036
S. I. Rermard Table 1. Examples of BAL used in diagnosis of cancer
Type of Cancer Primary lung Squamous Adenocarcinoma Large cell Small cell Bronchoalveolar Metastatic Solid tumors Breast Lymphangitic spread Hematologic malignancy Hodgkin's Non-Hodgkin's lymphoma Leukemia Waldenstrom's Myeloma Mycosis fungoides
Reference
7, 10, 21, 11 7, 10, 21, 11 7, 10, 21 7, 10, 21 8, 9 7 27 13 20, 23 14, 24, 25 7, 26 15 19 17
The flexible fiberoptic bronchoscope was first introduced by Ikeda to aid in diagnosis of lung cancer [1]. The major diagnostic technique to obtain material for the diagnosis of cancer was, and remains, transbronchoscopic biopsy. Nevertheless, bronchoalveolar lavage (BAL) can obtain material which permits the cytologic diagnosis of cancer. The criteria for the cytologic diagnosis of cancer in the lung are well established [2-4]. However, since BAL is often performed and interpreted by pulmonologists [5-7] who are not trained cytologists and because the stains most often used by pulmonologists do not always reveal cytologic detail, it is likely that the power of BAL to aid in the diagnosis of lung cancer has gone underappreciated. Recent studies indicate that bronchoalveolar lavage can aid in the diagnosis of cancer. The exact circumstances in which lavage will be most important and the diagnostic yield comparable to other techniques are, as yet, unanswered questions. Nevertheless, because of the ease of performance of the procedure and its relative safety, BAL must be considered one of the tools available to the clinician who must obtain material for the diagnosis of malignancy in the lung. In addition, it should be recognized that BAL performed for other reasons may reveal malignant cells in cases where cancer is not suspected. A rapidly enlarging collection of case reports and small series suggest that BAL can be of use in the diagnosis of a number of malignancies in the lung (Table 1). With regard to primary lung cancers, there are six series (including unpublished data contributed by the co-authors of this document) which address the issue of diagnostic yield of BAL (Table 2). Overall, the diagnostic yield was about 50% in these five series ranging from 35% to 69%. Only two of the centers categorized cases based on cell type. While the numbers are small,
BAL in the Diagnosis of Cancer
1037
Table 2. Diagnostic yield of bronchoalveolar lavage in lung cancer Contributor
No. of cases
No. with both BAL and diagnosis of cancer
No. of cases positive by BAL
Striz Worth Baglin et al. [12] Pirozynski Linder Schaberg et al. [38] Total
471 146 46 124 421 31
430 225 99 37 21 13 124 44 35 24 21 3 730 346 For sites, mean = 45 For cases, mean = 47
Percentage of cases positive by BAL 52 37 62 35 69 14
Table 3. Diagnostic yield for BAL in lung cancer Cell type* Bronchoalveolar cell carcinoma Small cell Squamous Adeno Large cell
Percentage yield (%) 11/12 10/35 2/3 9/49 7/10 11/20 12/15 0/5 3/7
92 32 27 66 25
* Data is reported for the various series available expressed as no. cases positive by BAL/no. cases of proven cancer undergoing BAL
the available data suggests that the diagnostic yield of BAL might be higher for bronchoalveolar cell carcinoma than for other cell types of primary pulmonary malignancy (Table 3). There are several important unanswered questions in these series, so it is not currently possible to compare lavage with other diagnostic techniques for malignancies in various distributions. It would be ideal to compare lavage with transbronchial biopsy, for example, for peripheral lesions, diffuse lesions and large central bronchoscopically visible lesions. Studies designed to address these issues are currently underway. While it is not possible to draw any firm conclusions, lavage can be of use in some cases of isolated peripheral nodules. It was also felt that lavage was particularly useful in diffuse lesions, such as those found with bronchoalveolar cell carcinoma. Thus, while lavage can clearly provide diagnostic material in a variety of clinical settings, its yield in specific settings remains to be determined. A second limitation of lavage is that the cytologic diagnosis of malignancy does not always correspond to the
1038
S . I . Rennard
histologic pattern [11]. Thus, in the series of Linder, cytology agreed with biopsy in only 80% of cases. The major difficulty was in distinguishing large cell undifferentiated carcinoma from adenocarcinoma. A similar problem occurs with the severe dysplastic changes that can develop in airway epithelial cells in a variety of clinical circumstances including pneumonia, viral infections and that following chemotherapy. These severe dysplastic changes can be very difficult to distinguish from malignant changes. These limitations of cytologic methods must be considered when bronchoalveolar lavage is used in the diagnosis of lung cancer. Several contributors to the current report have performed large series of BALs and have made a diagnosis of malignancy only very rarely. This has contributed to the impression that BAL has limited use in the diagnosis of cancer. There are several reasons which may explain the low diagnostic yield at these centers: 1) case selection may have been very different at different centers; 2) pulmonologists interested in performing BAL for specific research goals may not have processed lavage specimens in a manner to maximize yield for malignancy. Some investigators, for example, throw away the first aliquot returned, which is relatively enriched for bronchial material; for malignancies originating in the bronchial tree, this may represent the material with the highest diagnostic yield. In addition, many investigators filter the fluid through loose-weave gauze in order to remove mucus. Malignant cells are often present as clumps and may be removed by such filtration procedures. Finally, many investigators have performed the procedure in patients with malignancy in order to investigate immunologic abnormalities in these patients. They have intentionally lavaged sites not affected by the cancer. Thus, the relatively low diagnostic yield found by many investigators who have performed !avage for reasons other than to obtain diagnostic material, may reflect the interests of specific investigators rather than the utility of lavage to obtain material diagnostic of malignancy. A number of tumor markers have been studied in BAL [21, 28-35]. While there is considerable interest among investigators in such markers, none has proved to be diagnostic. Thus, the use of these markers must be considered a research tool at present. Whether these markers will be helpful in following patients on therapeutic protocoIs for malignancy is an interesting, but as yet unresolved, question. One investigator has suggested that cytologic assessment of malignancy can be used for a similar purpose. Again, this must be considered a research undertaking. However, inasmuch as BAL might provide a means to assess efficacy of novel therapeutic strategies in lung cancer, it may become an important adjunct in clinical studies. There is also a considerable interest in studying abnormalities in the patient with cancer. As such, a number of studies of bronchoalveolar lavage parameters have been undertaken in these patients [for reviews, please see Refs. 36, 37]. While these studies promise to provide some information as to why certain individuals develop malignancy and, perhaps, why these patients have increased incidences of lower respiratory tract infections, they are in fact research studies.
BAL in the Diagnosis of Cancer
1039
It is difficult to summarize current consensus regarding the use of bronchoalveolar lavage for the diagnosis of lung cancer. Current practices vary from never performing this procedure for this indication to routine performance. At institutions where this procedure is never performed, there is, obviously, no diagnostic yield associated with BAL. Centers where bronchoalveolar lavage has been found to be useful in the diagnosis of lung cancer are those centers where the procedure can be performed readily, the samples can be processed easily and trained personnel are available for the routine analysis of the specimens. In such a favorable setting, it would seem reasonable to include bronchoalveolar lavage in the diagnostic armamentarium used to evaluate patients for lung cancer. This is particularly so considering that the procedure has exceedingly low morbidity, and the increased cost over performing a bronchoscopy with other diagnostic procedures is relatively low.
References 1. Ikeda S (1974) Atlas of flexible bronchofiberscopy. City: University of Park Press, p 000 2. Johnston WW, Bossen EH (1981) Ten years of respiratory cytopathology at Duke University Medical Center: I. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, noting the significance of specimen number and type. Acta Cytol 25:103-107 3. Johnston WW, Bossen EH (1981) Ten years of respiratory cytopathology at Duke University Medical Center: II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer. Acta Cytol 25:499-505 4. Johnson WW, Frable WJ (1976) The cytopathology of the respiratory tract: a review. Am J Pathol 84:372-424 5- Reynolds HY (1987) State of the art: bronchoalveolar lavage. Am Rev Respir Dis 135:250-263 6. Reynolds HY, Chretian J (1984) Respiratory tract fluids: analysis of content and contemporary use of understanding lung diseases. DM 30:1-103 7. Linder J, Rennard S (1988) Bronchoalveolar Lavage. Chicago: ASCP Press, pp 1-196 8. Springmeyer SC Hackman R, Carlson JJ, McClellan JE (1983) Bronchiolo-alveolar cell carcinoma diagnosed by bronchoalveolar lavage. Chest 83:278-279 9. Sestini P, Rottoli L, Gotti G, Miracco C, Luzi P (1985) Bronchoalveolar lavage diagnosis of bronchiolo-alveolar carcinoma. Eur J Respir Dis 66:55-58 10. Korfhage L, Broghamer, WL, Richardson ME, Parker JE, Gilkey CM (1986) Pulmonary cytology in the posttherapeutic monitoring of patients with bronchogenic carcinoma. Acta Cytol 30:351-355 11. Linder J, Radio SJ, Robbins RA, Ghafouri M, Rennard SI (1987) Bronchoalveolar lavage in the cytologic diagnosis of carcinoma of the lung. Acta Cytol 31:796-801 12. Baglin JY, Danel C, Carnot F, Lacronique J, Jaubert F, Chretien J (1984) Interest of bronchoalveolar lavage (BAL) in the diagnosis of lung tumors with normal fiberoptic examination. Proceedings International Conference on Bronchoalveolar Lavage, Columbia, Maryland 13. FeduUo A J, Ettensohn DB (1985) Bronchoalveolar lavage in lymphangitic spread of adenocarcinoma to the lung. Chest 87:129-131 14. Davis WB, Gadek JE (1987) Detection of pulmonary lymphoma by bronchoalveolar lavage. Chest 91:787-790 t5. Kobayashi H, Ii K, Hizawa K, Maeda T (t985) Two cases of pulmonary Watdenstrom's macroglobulinemia. Chest 88:297-299 16. Levy H, Horak DA, Lewis MI (1988) The value of bronchial washings and bronchoalveolar lavage in the diagnosis of lymphangitic carcinomatosis. Chest 94:1028-1030
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