AMERICAN JOURNAL OF CLINICAL PATHOLOGY Editorial
Can Fine-Needle Aspiration Replace Open Biopsy in the Diagnosis of Palpable Breast Lesions?
145
allows definitive therapy to proceed on the basis of an FNA diagnosis of malignancy. Fine-needle aspiration's sensitivity for the detection of palpable carcinoma varies widely in reported series and is lower than that reported for frozen section evaluation.3"10 The sensitivity of a diagnostic procedure is determined by technical and interpretative limitations. The interpretative limits of FNA sensitivity are documented in this issue of the American Journal of Clinical Pathology by Rogers and Lee.'' They report that no combination of features accurately separated all benign and malignant cases in their study, and 13 of 16 cytologically difficult carcinomas were interpreted using cytologic analyses as fibroadenomas. Similar problems with sensitivity are reported by other authors.3,5"10 In addition, the sensitivity of FNA in many series is reduced by inadequate and limited sampling.5"10 Reported false-negative rates range from 0 to 35%.3 Falsenegative rates are considerably higher when the person performing the FNA has little experience with the technique than when the procedure is performed by an expert in the method. 3 Zarbo and colleagues,12 using data from a variety of practice settings, report an overall false-negative rate of 7.8% for FNA diagnosis of breast cancer. Although no precise data are available to determine the sensitivity rate of open biopsy, the FNA sensitivity rate of 92% is inferior to that achieved by frozen section analysis. 34 Given this level of sensitivity, the precise role FNA plays can be determined only after cost-benefit analysis and consideration of clinical setting. If FNA is used as the principal diagnostic technique to identify breast carcinoma, a small group of women will be underdiagnosed and the delay in diagnosis may allow potential progression of their disease. A primary concern among clinicians who choose not to use FNA for the investigation of breast masses is this potential for delay of diagnosis. Some proponents of FNA therefore have suggested the "triple diagnosis technique" as a strategy for improving diagnostic accuracy. 1314 This approach combines the findings of physical examination, mammography, and aspiration cytologic analysis to determine the diagnosis and assess the need for open biopsy. Using this
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Early diagnosis of breast cancer is a leading health care issue. In the past decade, detection of early, treatable cancers has increased as a result of patient education, selfexamination programs, and wider use of screening mammography. However, as the number of biopsies of suspicious lesions has increased, the cost of screening for breast cancer has also increased. More than half a million breast biopsies are performed yearly, and approximately 80% of these will reveal benign changes.' The need for cost containment has led to interest in alternative methods to open biopsy that could provide definitive diagnosis of breast cancer. Fine-needle aspiration (FNA) represents such an alternative technique. Approximately 60% of breast cancers are found as palpable masses2 and can be biopsied with FNA guided by simple palpation. The precise role of FNA in the diagnosis of breast disease is controversial. Clinicians diagnosing and treating breast disease have been slow to accept FNA because of concerns about its diagnostic accuracy and because open biopsy is a fairly simple procedure that serves as definitive therapy for many benign breast lesions. Furthermore, if a lump is judged to be cytologically benign by FNA but is not removed by open biopsy, it may cause concern at a later date when physicians may not have access to the previous FNA results. The clinical utility of a diagnostic procedure depends on the context in which it is used. A screening test should have as high a sensitivity rate as possible, although a lower specificity rate is acceptable in this setting. Tests used for definitive diagnosis require high sensitivity and specificity rates. If FNA is to replace open biopsy, it will no longer be a screening test but rather a diagnostic test, and it must diagnose breast lesions with a high degree of sensitivity and specificity. To compete with open biopsy as a diagnostic test, FNA must show a lower morbidity rate and significant cost savings. The specificity of FNA approaches that of frozen section analysis.3,4 Similar specificity data for open breast biopsy have not, to my knowledge, been reported. Reported specificity rates for FNA vary from 96% to 100%, with most large recent studies reporting false-positive rates of less than 0.5%.3,5~'° This high degree of diagnostic accuracy
146
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
A.J.C.P. •
perplastic and neoplastic breast disease are imprecise. In his study, 5 experienced surgical pathologists reviewing a series of 17 hyperplastic and in situ proliferations never achieved absolute agreement on the classification of the lesions. In six cases, diagnoses among the experts ranged from typical hyperplasia to carcinoma in situ. A similar spectrum of diagnoses must exist among general surgical pathologists for the interpretation of complex sclerosing lesions, sclerosing adenosis, intraductal papilloma, and invasive or in situ carcinoma. Given this degree of diagnostic imprecision using the "gold standard" of open biopsy, it is not surprising that there is less than 100% correlation between FNA and histologic findings. Both techniques have definable levels of diagnostic imprecision. Future studies investigating the sensitivity of open biopsy would aid in determining the relative sensitivity rates of FNA and open biopsy. Fine-needle aspiration cytologic examination represents a rapid and minimally invasive procedure for the diagnosis of breast nodules. Aspiration cytologic analysis can diagnose the majority of breast carcinomas at considerable savings compared with open biopsy. Because the sensitivity rate of FNA is slightly less than that of open biopsy, the technique should be used with this limitation in mind. Because of the reduced sensitivity rate of FNA, the technique appears most valuable when used for the diagnosis of breast disease in premenopausal women who are likely to return for follow-up visits. Most breast nodules in this age group are benign and it is most desirable to avoid surgical biopsy, with its concomitant higher cost, patient discomfort, and residual scarring and deformity. The lower morbidity rates of FNA increase patient acceptance as compared to open biopsy. Women who are unlikely to return for follow-up examinations should be studied by open biopsy. I recommend a modification of the strategy suggested by Grady and co-workers,15 in which the results of physical examination, mammography, and FNA are used to determine clinical management.3 If the nodule is cystic, all fluid is drawn off and cloudy or bloody fluid is examined microscopically. Residual solid areas are reaspirated. If the results of physical examination, mammography, and FNA reveal a benign lesion, the patient is followed clinically with physical reexamination every 3 to 6 months. When there is a diagnostic discordance between the physical examination, mammographic, or aspiration findings, open biopsy is performed. When physical examination, mammographic findings, and FNA indicate a malignant lesion, the patient is informed of her therapeutic options and prepared for definitive therapy. The incidence of breast carcinoma is relatively high in postmenopausal women, increasing the possibility of falsenegative FNA results. Postmenopausal patients should be followed closely. If they are unlikely to comply, the nodule ;ust 1992
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
strategy, if all three findings suggest malignancy the patient is referred for definitive therapy, whereas if all three components indicate benignancy, the patient is followed clinically. Open biopsy is performed if there is discordance between physical, mammographic, or cytologic findings. This "triple diagnosis" strategy reduces the number of open biopsies by 50% while increasing the diagnostic sensitivity rate to 98.8%. This level of diagnostic sensitivity parallels that achieved by frozen section3,4 and open biopsy.15 A crucial issue in the decision to use FNA and the "triple diagnosis" technique is the cost-benefit ratio for patients with negative triple diagnosis results. These patients are followed clinically and exposed to a potential delay in diagnosis. I am unaware of any recent cost-benefit analyses using modern statistical methods combined with current data on patient prognosis and the effects of delay in diagnosis, but Lannin and associates16 report significant cost savings when FNA is used as the initial diagnostic test. In this study, FNA is cost-effective, saving $104 per case compared with routine outpatient biopsy, and $393 compared with routine inpatient biopsy. Our experience suggests a cost savings two to three times greater than this. Statistical analysis shows that FNA remains cost-effective even when its sensitivity rate decreases to 37% and the specificity rate decreases to as low as 80%.16 In addition to the monetary savings, FNA offers the advantages of rapid diagnosis with minimal discomfort. Rapid same-day diagnosis allows patient counseling about treatment options during the initial visit. Because FNA is a minimally invasive procedure and leaves no visible scars, it represents an excellent technique to diagnose breast disease in young women with multiple nodules. Multiple traditional open biopsies in such patients can cause considerable patient anguish and leave cosmetically undesirable scars. Furthermore, postbiopsy changes may mimic carcinoma on mammograms, resulting in future diagnostic uncertainty and additional unnecessary biopsies.17 Another difficulty Rogers and Lee raise in their study is the nonspecificity of criteria to diagnose proliferative breast disease." Clinicians recognize the imperfect accuracy and imprecise diagnostic criteria of FNA but often are unaware that there are similar deficiencies in the accuracy and criteria used for the evaluation of frozen and permanent section preparations. The "gold standard" of open biopsy (against which all other diagnostic techniques are judged) is in itself imperfect. There are as-yet poorly defined false-negative and false-positive rates associated with excisional biopsy. Some authors have estimated a false-negative rate of 1.4% for open biopsy.' 5 Open biopsy is subject to sampling and interpretive errors. Rosai18 illustrates that current histologic criteria to diagnose hy-
AMERICAN JOURNAL OF CLINICAL PATHOLOGY Editorial should be excised. Using this modification of the scheme of Grady and co-workers,15 needle aspiration cytologic analysis of palpable nodules can achieve significant monetary savings, a reduction in patient morbidity, an increased speed of diagnosis, and increased opportunity for preoperative patient counseling without reduction in diagnostic accuracy or compromise of patient prognosis. LESTER J. LAYFIELD, M.D. Department of Pathology Duke University Medical Center Durham, North Carolina
References
6. Cornillot M, Verhaeghe M, Cappelaere P, Clay A. Place de la cytologic par ponction dans le diagnostic des tumeurs du sein. Presse Med 1971;79:1813-1819. 7. Kline TS, Joshi LP, Neal HS. Fine-needle aspiration of the breast: Diagnoses and pitfalls. A review of 3545 cases. Cancer 1979;44: 1458-1464. 8. Pilotti S, Rilke F, Delpiano C, Di Pietro S. Problems in fine-needle aspiration biopsy: Cytology of clinically or mammographically uncertain breast tumors. Tumori 1982;68:407-412. 9. Zajdela A, Ghossein NA, Pilleron JP, Ennuyer A. The value of aspiration cytology in the diagnosis of breast cancer. Experience at the Foundation Curie. Cancer 1975;35:499-506. 10. Wollenberg NJ, Caya JG, Clowry hi. Fine-needle aspiration cytology of the breast. A review of 321 cases with statistical evaluation. ActaCytol 1985;29:425-429. 11. Rogers LA, Lee KR. Breast carcinoma simulating fibroadenoma or fibrocystic change by FNA: A study of 16 cases. Am J Clin Pathol 1992;98:155-160. 12. Zarbo RJ, Howanitz PJ, Bachner P. Interinstitutional comparison of performance in breast fine-needle aspiration cytology. A Qprobe quality indicator study. Arch Pathol Lab Med 1991:115: 743-750. 13. Hermansen C, Poulsen HS, Jensen J, et al. Diagnostic reliability of combined physical examination, mammography and fine needle puncture ("triple-test") in breast tumors. A prospective study. Cancer 1987;60:1866-1871. 14. Kreuzer G, Boquoi E. Aspiration biopsy cytology, mammography and clinical exploration: A modern set-up in diagnosis of tumors of the breast. Acta Cytol 1976;20:319-323. 15. Grady D, Hodgkin ML, Goodson WH. The lumpy breast. West J Med 1988;149:226-229. 16. Lannin DR, Silverman JF, Pories WJ, Walker C. Cost effectiveness of fine-needle biopsy of the breast. Ann Surg 1986;203:474-480. 17. Sickles EA, Herzog KA. Intramammary scar tissue: A mimic of the mammographic appearance of carcinoma. AJR 1980; 135:349352. 18. Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol 1991;15:209-221.
Vol. 98 • No. 2
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
1. Winchester DP, Senen S, Immerman S, Blum M. A systemic approach to the evaluation and management of breast masses. Cancer 1983;51:2535-2540. 2. Rosato FE, Rosenberg AL. Examination techniques: Role of the physician and patient in evaluating breast diseases. In: Bland KZ, Copeland III EM, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders, 1991, p410. 3. Layfield LI, Glasgow BJ, Cramer H. Fine-needle aspiration in the management of breast masses. In: Rosen PP, Fechner RE, eds. Pathology Annual: Nineteen Eighty-Nine, Part 2. Norwalk, CT: Appleton and Lange, 1989, 23-62. 4. Thomas PA, Vazquez MF, Waisman J. Comparison of fine-needle aspiration and frozen section of palpable mammary lesions. Mod Pathol 1990;3:570-574. 5. Deschens L, Fabia J, Meisels A, et al. Fine-needle aspiration in the management of palpable breast lesions. Can J Surg 1978;21:417419.
147
Can Fine-Needle Aspiration Replace Open Biopsy in the Diagnosis of Palpable Breast Lesions?
145
allows definitive therapy to proceed on the basis of an FNA diagnosis of malignancy. Fine-needle aspiration's sensitivity for the detection of palpable carcinoma varies widely in reported series and is lower than that reported for frozen section evaluation.3"10 The sensitivity of a diagnostic procedure is determined by technical and interpretative limitations. The interpretative limits of FNA sensitivity are documented in this issue of the American Journal of Clinical Pathology by Rogers and Lee.'' They report that no combination of features accurately separated all benign and malignant cases in their study, and 13 of 16 cytologically difficult carcinomas were interpreted using cytologic analyses as fibroadenomas. Similar problems with sensitivity are reported by other authors.3,5"10 In addition, the sensitivity of FNA in many series is reduced by inadequate and limited sampling.5"10 Reported false-negative rates range from 0 to 35%.3 Falsenegative rates are considerably higher when the person performing the FNA has little experience with the technique than when the procedure is performed by an expert in the method. 3 Zarbo and colleagues,12 using data from a variety of practice settings, report an overall false-negative rate of 7.8% for FNA diagnosis of breast cancer. Although no precise data are available to determine the sensitivity rate of open biopsy, the FNA sensitivity rate of 92% is inferior to that achieved by frozen section analysis. 34 Given this level of sensitivity, the precise role FNA plays can be determined only after cost-benefit analysis and consideration of clinical setting. If FNA is used as the principal diagnostic technique to identify breast carcinoma, a small group of women will be underdiagnosed and the delay in diagnosis may allow potential progression of their disease. A primary concern among clinicians who choose not to use FNA for the investigation of breast masses is this potential for delay of diagnosis. Some proponents of FNA therefore have suggested the "triple diagnosis technique" as a strategy for improving diagnostic accuracy. 1314 This approach combines the findings of physical examination, mammography, and aspiration cytologic analysis to determine the diagnosis and assess the need for open biopsy. Using this
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Early diagnosis of breast cancer is a leading health care issue. In the past decade, detection of early, treatable cancers has increased as a result of patient education, selfexamination programs, and wider use of screening mammography. However, as the number of biopsies of suspicious lesions has increased, the cost of screening for breast cancer has also increased. More than half a million breast biopsies are performed yearly, and approximately 80% of these will reveal benign changes.' The need for cost containment has led to interest in alternative methods to open biopsy that could provide definitive diagnosis of breast cancer. Fine-needle aspiration (FNA) represents such an alternative technique. Approximately 60% of breast cancers are found as palpable masses2 and can be biopsied with FNA guided by simple palpation. The precise role of FNA in the diagnosis of breast disease is controversial. Clinicians diagnosing and treating breast disease have been slow to accept FNA because of concerns about its diagnostic accuracy and because open biopsy is a fairly simple procedure that serves as definitive therapy for many benign breast lesions. Furthermore, if a lump is judged to be cytologically benign by FNA but is not removed by open biopsy, it may cause concern at a later date when physicians may not have access to the previous FNA results. The clinical utility of a diagnostic procedure depends on the context in which it is used. A screening test should have as high a sensitivity rate as possible, although a lower specificity rate is acceptable in this setting. Tests used for definitive diagnosis require high sensitivity and specificity rates. If FNA is to replace open biopsy, it will no longer be a screening test but rather a diagnostic test, and it must diagnose breast lesions with a high degree of sensitivity and specificity. To compete with open biopsy as a diagnostic test, FNA must show a lower morbidity rate and significant cost savings. The specificity of FNA approaches that of frozen section analysis.3,4 Similar specificity data for open breast biopsy have not, to my knowledge, been reported. Reported specificity rates for FNA vary from 96% to 100%, with most large recent studies reporting false-positive rates of less than 0.5%.3,5~'° This high degree of diagnostic accuracy
146
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
A.J.C.P. •
perplastic and neoplastic breast disease are imprecise. In his study, 5 experienced surgical pathologists reviewing a series of 17 hyperplastic and in situ proliferations never achieved absolute agreement on the classification of the lesions. In six cases, diagnoses among the experts ranged from typical hyperplasia to carcinoma in situ. A similar spectrum of diagnoses must exist among general surgical pathologists for the interpretation of complex sclerosing lesions, sclerosing adenosis, intraductal papilloma, and invasive or in situ carcinoma. Given this degree of diagnostic imprecision using the "gold standard" of open biopsy, it is not surprising that there is less than 100% correlation between FNA and histologic findings. Both techniques have definable levels of diagnostic imprecision. Future studies investigating the sensitivity of open biopsy would aid in determining the relative sensitivity rates of FNA and open biopsy. Fine-needle aspiration cytologic examination represents a rapid and minimally invasive procedure for the diagnosis of breast nodules. Aspiration cytologic analysis can diagnose the majority of breast carcinomas at considerable savings compared with open biopsy. Because the sensitivity rate of FNA is slightly less than that of open biopsy, the technique should be used with this limitation in mind. Because of the reduced sensitivity rate of FNA, the technique appears most valuable when used for the diagnosis of breast disease in premenopausal women who are likely to return for follow-up visits. Most breast nodules in this age group are benign and it is most desirable to avoid surgical biopsy, with its concomitant higher cost, patient discomfort, and residual scarring and deformity. The lower morbidity rates of FNA increase patient acceptance as compared to open biopsy. Women who are unlikely to return for follow-up examinations should be studied by open biopsy. I recommend a modification of the strategy suggested by Grady and co-workers,15 in which the results of physical examination, mammography, and FNA are used to determine clinical management.3 If the nodule is cystic, all fluid is drawn off and cloudy or bloody fluid is examined microscopically. Residual solid areas are reaspirated. If the results of physical examination, mammography, and FNA reveal a benign lesion, the patient is followed clinically with physical reexamination every 3 to 6 months. When there is a diagnostic discordance between the physical examination, mammographic, or aspiration findings, open biopsy is performed. When physical examination, mammographic findings, and FNA indicate a malignant lesion, the patient is informed of her therapeutic options and prepared for definitive therapy. The incidence of breast carcinoma is relatively high in postmenopausal women, increasing the possibility of falsenegative FNA results. Postmenopausal patients should be followed closely. If they are unlikely to comply, the nodule ;ust 1992
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
strategy, if all three findings suggest malignancy the patient is referred for definitive therapy, whereas if all three components indicate benignancy, the patient is followed clinically. Open biopsy is performed if there is discordance between physical, mammographic, or cytologic findings. This "triple diagnosis" strategy reduces the number of open biopsies by 50% while increasing the diagnostic sensitivity rate to 98.8%. This level of diagnostic sensitivity parallels that achieved by frozen section3,4 and open biopsy.15 A crucial issue in the decision to use FNA and the "triple diagnosis" technique is the cost-benefit ratio for patients with negative triple diagnosis results. These patients are followed clinically and exposed to a potential delay in diagnosis. I am unaware of any recent cost-benefit analyses using modern statistical methods combined with current data on patient prognosis and the effects of delay in diagnosis, but Lannin and associates16 report significant cost savings when FNA is used as the initial diagnostic test. In this study, FNA is cost-effective, saving $104 per case compared with routine outpatient biopsy, and $393 compared with routine inpatient biopsy. Our experience suggests a cost savings two to three times greater than this. Statistical analysis shows that FNA remains cost-effective even when its sensitivity rate decreases to 37% and the specificity rate decreases to as low as 80%.16 In addition to the monetary savings, FNA offers the advantages of rapid diagnosis with minimal discomfort. Rapid same-day diagnosis allows patient counseling about treatment options during the initial visit. Because FNA is a minimally invasive procedure and leaves no visible scars, it represents an excellent technique to diagnose breast disease in young women with multiple nodules. Multiple traditional open biopsies in such patients can cause considerable patient anguish and leave cosmetically undesirable scars. Furthermore, postbiopsy changes may mimic carcinoma on mammograms, resulting in future diagnostic uncertainty and additional unnecessary biopsies.17 Another difficulty Rogers and Lee raise in their study is the nonspecificity of criteria to diagnose proliferative breast disease." Clinicians recognize the imperfect accuracy and imprecise diagnostic criteria of FNA but often are unaware that there are similar deficiencies in the accuracy and criteria used for the evaluation of frozen and permanent section preparations. The "gold standard" of open biopsy (against which all other diagnostic techniques are judged) is in itself imperfect. There are as-yet poorly defined false-negative and false-positive rates associated with excisional biopsy. Some authors have estimated a false-negative rate of 1.4% for open biopsy.' 5 Open biopsy is subject to sampling and interpretive errors. Rosai18 illustrates that current histologic criteria to diagnose hy-
AMERICAN JOURNAL OF CLINICAL PATHOLOGY Editorial should be excised. Using this modification of the scheme of Grady and co-workers,15 needle aspiration cytologic analysis of palpable nodules can achieve significant monetary savings, a reduction in patient morbidity, an increased speed of diagnosis, and increased opportunity for preoperative patient counseling without reduction in diagnostic accuracy or compromise of patient prognosis. LESTER J. LAYFIELD, M.D. Department of Pathology Duke University Medical Center Durham, North Carolina
References
6. Cornillot M, Verhaeghe M, Cappelaere P, Clay A. Place de la cytologic par ponction dans le diagnostic des tumeurs du sein. Presse Med 1971;79:1813-1819. 7. Kline TS, Joshi LP, Neal HS. Fine-needle aspiration of the breast: Diagnoses and pitfalls. A review of 3545 cases. Cancer 1979;44: 1458-1464. 8. Pilotti S, Rilke F, Delpiano C, Di Pietro S. Problems in fine-needle aspiration biopsy: Cytology of clinically or mammographically uncertain breast tumors. Tumori 1982;68:407-412. 9. Zajdela A, Ghossein NA, Pilleron JP, Ennuyer A. The value of aspiration cytology in the diagnosis of breast cancer. Experience at the Foundation Curie. Cancer 1975;35:499-506. 10. Wollenberg NJ, Caya JG, Clowry hi. Fine-needle aspiration cytology of the breast. A review of 321 cases with statistical evaluation. ActaCytol 1985;29:425-429. 11. Rogers LA, Lee KR. Breast carcinoma simulating fibroadenoma or fibrocystic change by FNA: A study of 16 cases. Am J Clin Pathol 1992;98:155-160. 12. Zarbo RJ, Howanitz PJ, Bachner P. Interinstitutional comparison of performance in breast fine-needle aspiration cytology. A Qprobe quality indicator study. Arch Pathol Lab Med 1991:115: 743-750. 13. Hermansen C, Poulsen HS, Jensen J, et al. Diagnostic reliability of combined physical examination, mammography and fine needle puncture ("triple-test") in breast tumors. A prospective study. Cancer 1987;60:1866-1871. 14. Kreuzer G, Boquoi E. Aspiration biopsy cytology, mammography and clinical exploration: A modern set-up in diagnosis of tumors of the breast. Acta Cytol 1976;20:319-323. 15. Grady D, Hodgkin ML, Goodson WH. The lumpy breast. West J Med 1988;149:226-229. 16. Lannin DR, Silverman JF, Pories WJ, Walker C. Cost effectiveness of fine-needle biopsy of the breast. Ann Surg 1986;203:474-480. 17. Sickles EA, Herzog KA. Intramammary scar tissue: A mimic of the mammographic appearance of carcinoma. AJR 1980; 135:349352. 18. Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol 1991;15:209-221.
Vol. 98 • No. 2
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
1. Winchester DP, Senen S, Immerman S, Blum M. A systemic approach to the evaluation and management of breast masses. Cancer 1983;51:2535-2540. 2. Rosato FE, Rosenberg AL. Examination techniques: Role of the physician and patient in evaluating breast diseases. In: Bland KZ, Copeland III EM, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders, 1991, p410. 3. Layfield LI, Glasgow BJ, Cramer H. Fine-needle aspiration in the management of breast masses. In: Rosen PP, Fechner RE, eds. Pathology Annual: Nineteen Eighty-Nine, Part 2. Norwalk, CT: Appleton and Lange, 1989, 23-62. 4. Thomas PA, Vazquez MF, Waisman J. Comparison of fine-needle aspiration and frozen section of palpable mammary lesions. Mod Pathol 1990;3:570-574. 5. Deschens L, Fabia J, Meisels A, et al. Fine-needle aspiration in the management of palpable breast lesions. Can J Surg 1978;21:417419.
147
