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Carcinoma In Situ of the Breast
Symposium on Recent Advances in Surgery
Carcinoma In Situ of the Breast
William D. Shorey, MD.*
In 1971, more than 65,000 new cases of carcinoma of the breast will be diagnosed. 3,24 Of that number, about the same percentage of patients will die of cancer of the breast as in the time of Halsted. 2 The paradox that 85 to 90 per cent of tumors are found by the patients themselves, and then only with an average size of 5 cm., must be contrasted with the availability of the organ sturcture for examination and inspection. From studies done by numerous authors!. 6, 9, 18,27 it is apparent that tumors of the breast, as in other related hormonally controlled structures such as the cervix,4 do not develop in a short period of time, but rather over a period of many years to decades. It is therefore significant to consider the problem of those changes which occur in the breast which may be considered as "in situ" carcinomas and their relationship to the possible progression to invasive carcinomas or separate, and possibly cellularly different, carcinomas. In the past decade the combination of mammography with biopsy of lesions suspicious either radiographically or on physical examination has given us a greater insight as to the frequency and significance of this condition. The types of "in situ" carcinomas to be discussed are those as outlined by Stewart.29 Lobular Carcinoma In Situ Since the original description of lobular carcinoma in situ by Foote and Stewart5 in 1941, numerous reports of this form of cancer of the breast have been published. 6 , 11.12. 17.35 In the past 2 years, the incidence of lobular carcinoma in situ in our hospital has been 8 per cent. 23 This compares with a incidence of 10.2 per cent reported by Newman21 in a series of 1436 primary carcinomas of the breast. The average age at the time of initial diagnosis was from 44 to 48.3 years, with a range of 29 to 83 years. 22 As pointed out by Foote and Stewart, this diagnosis of lobular carcinoma, either in situ or invasive, is a pathologist's diagnosis. 5 The diagnosis should not be made on a frozen section, but rather on permanent sections of suspicious areas. Clinically the lesion is of small size and *Associate Professor of Surgery. University of Illinois College of MediCine; Attending Surgeon, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois Surgical Clinics of North America- Vol. 51, No.1, February 1971
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is found in biopsies in which the primary pathology is that of "chronic cystic mastitis." Lobular carcinoma is multifocal and secondary foci will be found in the majority (70 per cent) of breasts subject to mastectomy of the ipsilateral breastY The propensity for this condition to occur simultaneously in both breasts has been recognized for many year~. Newman has shown that random biopsies of the upper outer quadrant of the contralateral breast at the time of diagnosis of the primary lesion will reveal bilateral disease in 23 per cent. 22 McDivitt reports an incidence greater than 30 per cent.17 Urban33 reports a somewhat higher figure of 59 per cent. It has been shown that lobular carcinoma in situ, if treated only by local excisional biopsy, will develop into infiltrating carcinoma in a significantly high percentage of cases. McDivitt et aP6 report that the incidence of ipsilateral carcinoma at 5 years is 8 per cent, but rises to 35 per cent at 20 years. For the contralateral breast, the incidence is 10 per cent in 10 years, increasing to 25 per cent in 20 years. In recent years the diagnosis of lobular carcinoma in situ has been made prior to biopsy in an increasing number of cases. Mammography, as shown by Snyder 6 and Hatter,12 may point out suspicious areas of calcification in otherwise normal breasts, or in relation to areas more suggestive of chronic cystic mastitis. The cooperation of radiologist, pathologist, and surgeon will insure that the proper area or areas for biopsy are successfully removed. Lobular carcinoma occurs in situ in 40 to 50 per cent of all cases of lobular carcinoma. If, on permanent section, the lesion is shown to be an infiltrating process, radical mastectomy should be performed. 29 Theoretically, if the lesion is found to be lobular carcinoma in situ, simple mastectomy should and has produced 100 per cent control of the disease. 17 However, a review of sections taken from a breast following simple mastectomy has frequently shown areas of invasion in sites other than that removed at the first biopsy. It is therefore the consensus of most authors l7 . 22 that simple mastectomy should be combined with a lower axillary dissection. If, at the table, the axillary dissection should appear or prove to show lymph node involvement, the procedure should be converted into a radical mastectomy. . The prognosis for survival of truly lobular carcinoma in situ with such a simple mastectomy is 100 per cent. For lobular carcinoma with invasion without positive nodes, Newman reports 31 of 36 patients alive at 5 years, and for those with positive nodes, 18 of 37 alive at 5 years. McDivitt reports a 42 per cent 10-year survival rate in his patients with positive lymphatic involvement. Because of the bilaterality of this condition, a biopsy selected by mammograph, or, if no radiographic abnormality exists, a random biopsy of the upper outer quadrant, should be carried out following or concurrently with the treatment of the primary breast. A negative biopsy alone should be the basis for a long and close follow-up of these patients, combined with periodic mammographic examination. Intraductal Carcinoma In Situ This has been recognized as a premalignant lesion since the work of Foote and Stewart in 1945.6 The diagnosis has been universally
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recognized by the criterion first laid down by Foote and Stewart and confirmed by other pathologists. L 10, 19,27 The treatment of this condition is based on the fact that it is extremely difficult to be absolutely certain, even on multiple sections, that no evidence of invasion exists beyond the basement membrane. Gallagar and Martin9 report two cases of intraductal carcinoma in situ with metastasis to axillary lymph nodes in which multiple sections of whole breast mounts at 0.5 mm. thickness failed to show the areas of invasion. It is obvious that the diagnosis of intraductal carcinoma, whether in situ or invasive, cannot be made on frozen section unless an obvious area of invasion can be suspected macroscopically and confirmed by frozen section. The usual course of events will be that the diagnosis is suspected on frozen section and confirmed 24 hours later by permanent sections-either as in situ or invasive carcinoma. If invasive, radical mastectomy is the procedure of choice. If in situ, simple or subcutaneous mastectomy should suffice to control the disease process. Biopsy of the contralateral breast should also be done: since this type of breast lesion is bilateral in 32 to 40 per cent of the cases. 33 However, lacking the facilities for semi-serial sections, a focus of infiltrating carcinoma is most difficult to exclude. In case of any doubt whatsoever, radical mastectomy is the procedure of choice and will give the highest percentage of longer than 10 year survival free of disease. 2o A variance of intraductal carcinoma is Paget's disease. This is defined by Muir2° as an intraductal carcinoma of the large ducts at or just beneath the nipple. It constitutes 1 to 4 per cent of all carcinomas of the breast. This disease entity is first recognized by an eczematoid thickening of the nipple, with or without retraction. In the earlier stages and in its in situ form, no mass is generally palpable. Mammography is of little value in diagnosis, which can only be made by biopsy. If a mass beneath or in the nipple is present to palpation, local invasion must be assumed and the lesion treated with a radical mastectomy or simple mastectomy with axillary dissection following biopsy. Those lesions truly in situ, with no evidence of invasion beyond the basement membrane, may be adequately treated in the postmenopausal patient by simple mastectomy. The survival of patients with in situ lesions is reported as 96 per cent in a series of 27 patients treated by simple mastectomy. Among postmenopausal patients with lymph node involvement, 7 of 23 died in 5 years. In premenopausal patients, all with positive nodes died in the same period, and five of nine died when the nodes were not involved with tumor.22 It must be emphasized that the prognosis of Paget's disease is not to be taken lightly. Toker 2 has shown by 1050 serial sections of one case of Paget's disease that the cells which caused the invasion of the nipple arose in a carcinoma 3 cm. in depth from the nipple. This occurred through intra-epithelial spread by permeation in the wall of the duct. It is difficult to conceive of this type of involvement as other than invasively malignant. In a series reported by McDivitt et alP a mass was clinically present in the breast at or adjacent to the diseased nipple in only 24 of 38 cases in which it was later proven pathologically that a mass was present. Therefore, I feel that an "in situ" diagnosis of Paget's disease should be
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confirmed by permanent sections prior to treatment by simple mastectomy. All others should be treated with a radical dissection. If there are positive axillary nodes, an extended radical mastectomy as described by Urban34 or radiation to the internal mammary chain should be considered for complete therapy of this lesion. Chronic Cystic Mastitis Should chronic cystic mastitis be considered as a premalignant, pre-in situ carcinoma? Foote and Stewart point out that the term chronic cystic mastitis is too broad, includes too many morphologic patterns, and that any point may be made by proper selection of criteria. However, since the work of Warren,37 a growing number of authors have pointed out the coexistence of forms of specific changes in the breast, which are commonly diagnosed "chronic cystic mastitis," with either in situ or invasive carcinoma. Gallagail has shown in 100 per cent of 60 breasts with primary carcinomas that there are concomitant and separate changes in the ductal epithelium. These changes range from simple hyperplasia, to hyperplasia with atypical cells, to in situ carcinoma. This is, in general, a diffuse process in the breast. Tellum31 reports that his series shows 3 to 5 times the normal incidence of carcinoma in women who have had chronic cystic mastitis. In a series of 90 women over 60 years of age, 54 had intraductal carcinoma adjacent to or removed from the primary carcinoma. In 24 of this group there was marked ductal hyperplasia. Similar findings are reported by Steinhoff and Black,28 who point out that lobular and papillomatous changes seem to be the ones most commonly associated with primary carcinoma. Both Stein 27 and Gallagar 9 suggest that there is a probability that breast tissue may pass through a hyperplastic stage with atypism on the path to an in situ or invasive carcinoma. They stress, however, that this progression is a nonobligate change. Changes from atypism in ductal or lobular structures to normal have frequently been recorded. The mechanism of this is unknown. These epithelial changes may take the form of papillomatous growths, which have been categorized as intraductal papilloma, intraductal papillomatosis, or epithelial hyperplasia with or without atypism. The relationships of these changes to carcinoma have been extensively discussed by many authors. 1, 6, 9,10,11,13,14, 18, 19,23 In my opinion it is probably accurate to state that women who have such changes constitute, from a pathological point of view, a group which has a higher risk of developing an in situ cancer or an invasive lesion. Further, if a patient should have two or more biopsies of suspicious lesions, the degree of dysplasia of the ductal elements should be carefully recorded. If there are changes of a progressive nature toward atypism, the risk of the patient developing a cancer must be considered as increasing. At the Presbyterian-St. Luke's Hospital the form shown in Figure 1 has been adopted to record certain types of specific cellular abnormalities in all breast biopsies or mastectomy specimens. This is designed to
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BREAST PATHOLOGY REPORT Specimen from: Right Breast 1 Left Breast 2 Date of operation: I I Mo I Day I Yr CODE
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DIAGNOSIS (Circle applicable code numbers below)
A. FIBROCYSTIC DISEASE
1110 Sclerosis, inflammation, cysts, stasis, and ductal ectasia 1210 Hyperplasia of duct epithelium-slight 1220 Hyperplasia of duct epithelium-moderate 1230 Hyperplasia of duct epithelium-severe 1240 Hyperplasia of duct epithelium-atypical 1310 Lobular hyperplasia-slight 1320 Lobular hyperplasia-moderate 1330 Lobular hyperplasia-severe 1340 Lobular hyperplasia-atypical 1411 Duct papillomatosis - solitary, typical 1412 Duct papillomatosis-solitary, atypical 1421 Duct papillomatosis-multiple, typical 1422 Duct papillomatosis-multiple, atypical 1510 Sclerosing adenosis-focal 1520 Sclerosing adenosis-diffuse 1610 Blunt duct adenosis 1710 Apocrine metaplasia 1810 Fibroadenomatous change 1910 Fat necrosis (nontraumatic) B. MALIGNANT NEOPLASMS 2111 NOninfiltrating, papillary, solitary 2112 Noninfiltrating, papillary, multiple 2121 Noninfiltrating, ductal 2131 Noninfiltrating, lobular 2211 Infiltrating, papillary, solitary 2212 Infiltrating, papillary, multiple 2221 Infiltrating, ductal 2231 Infiltrating, comedo carcinoma (with central necrosis) 2241 Infiltrating, medullary 2251 Infiltrating, mucinous 2261 Infiltrating, lobular 2271 Infiltrating, epidermoid 3110 3120 3210 3310 3410
Fibroadenoma, benign Fibroadenoma, malignant Mesodermal (e.g., sarcoma) Reticular (e.g., lymphoma) Epithelial (e.g., sweat gland, adenoid cystic)
C. LYMPH NODES Total number Number positive _ _ __ Figure 1
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be placed in a computer for easy recall to facilitate the review of an individual patient's progression as well as for statistical study. In all patients with a suspicious lesion, generous excisional biopsy is recommended. This is not only to insure the complete removal of the primary pathology but also to give to the surgeon and pathologist an understanding of the surrounding "normal" breast tissue left behind. For those cases in which an intraductal papilloma is suggested by a localized serous or bloody discharge, a quadrant excision is the procedure of choice. 1 The suspicion of a papillomatous process, either single or multiple, is a contraindication to frozen-s~ction diagnosis. Permanent sections will afford much better definition on such specimens and the chance of losing the papilloma will be avoided. If the biopsy should reveal significant cellular atypism of the ductal cells, either in the form of a single papilloma or multiple papillomatolls foci, the patient as a whole should be evaluated. The family history of carcinoma, age, and number of previous biopsies must be considered in relation to the patient's emotional status. Though it must be emphasized, as pointed out by Foote and Stewart,S that there must be many more studies of a prospective nature to prove that there is a causal relationship between ductal atypism and cancer, the risk of malignancy is always present and may well be increased. It may, in individual cases, seem wise to suggest bilateral simple mastectomy in these selected cases. With the development of more aesthetically satisfactory breast prostheses, subcutaneous mastectomies are being utilized, followed at a later date by a reconstructive procedure. It must be emphasized that meticulous care must be taken to remove the entire breast structures in either procedure, especially the "tail of Spence." For all patients not treated by primary mastectomy, it is our practice to follow them at frequent intervals, especially those who have significant cellular atypia in,their lobular or ductal structures. A team of surgeon, pathologist, and radiologist must work together to locate and remove areas of suspicious nature, suggested either by palpation or mammography. It is hoped that through this effort,- carried out on a continuing basis, a higher proportion of in situ lesions may be identified and, through proper treatment, may result in a decrease in the mortality statistics of this disease.
SUMMARY . Lobular carcinoma has few physical signs. It is a diagnosis made pathologically on permanent section. Recently mammography has proven helpful in suggesting its presence. If it occurs in situ, it should be removed by a mastectomy with low axillary dissection. If it is invasive, on biopsy or at the time of axillary dissection, radical dissection with or without postoperative irradiation therapy has given the best results. Intraductal carcinoma in situ is again a pathologist's diagnosis. The possibility of it being invasive is higher than in lobular carcinoma.
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Treatment is therefore more often of a raqical nature. Paget's disease may be considered a variant of this condition. The changes of ductal epithelium toward atypism, seen only too often in otherwise typical "chronic mastitis," may be a pre-pre-in situ lesion. These changes are reversible in many patients. A team approach of surgeon, diagnostic radiologist, and pathologist affords the basis of a rational approach to the proper treatment of these patients on an individual basis. The importance of a prolonged prospective study of this condition is emphasized.
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ACKNOWLEDGMENT
I wish to express my gratitude to Dr. Edmund Pellettiere for the use of his unpublished data.
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REFERENCES 1. Buhl-Jorgensen, s. E., et al.: Cancer risk in intraductal papilloma and papillomatosis. Surg. Gynec. Obstet., 127:1307-1312, 1968. 2. Cutter, S. J., and Connelly, R. R.: Mammary cancer trends. Cancer, 23:767-771,1969. 3. Dunn, J. E., Jr.: Epidemiology and possible identification of high risk groups that could develop cancer of the breast. Cancer, 23: 775-780, 1969. . 4. Fluhmann, C. F.: The Cervix Uteri and Its Diseases. Philadelphia, W. B. Saunders Co., 1961. 5. Foote, F. W., and Stewart, F. W.: Lobular carcinoma in situ. Amer. J. Path., 17:491-496, 1941. 6. Foote, F. W., and Stewart, F. W.: Comparative studies of cancerous versus noncancerous breasts. II. Rate of so-called chronic cystic mastitis in mammary carcinogenesis. Ann. Surg., 121 :197-221,1945. 7. Frantz, V. K., Pickren, J. W., Melcher, G. W., and Auchencloss, H., Jr.: Incidence of chronic cystic mastitis in so-called normal breasts; study based on 225 post mortem examinations. Cancer, 4:762,1951. 8. Funderburk, W. W., and Syphax, B.: Evaluation of nipple discharge. Cancer, 24:12901296,1969. 9. Gallagar, H., and Martin, J. E.: Early phases in the development of breast cancer. Cancer, 24:1170-1178,1969 . 10. Gillis, D. A., Dockerty, M. B., and Clagett, O. T.: Preinvasive intraductal carcinoma of breast. Surg. Gynec. Obstet., 110:555-559, 1960. 11. Haagenson, C. D.: Lobular carcinoma of the breast. Clin. Obstet. Gynec., 5:1093-1101, 1962. 12. Hatter, R. V. P., Snyder, R. E., Lucas, J. C., Foote, F. W., and Farrow, J. H.: Clinical and pathological correlations with mammographic findings in lobular carcinoma in situ. Cancer, 23:826-839,1969. 13. Humphery, L. J., and Swerdlow, M. A.: Relationship of benign breast disease to carcinoma ofthe breast. Surgery, 52:841-846,1962. 14. Humphery, L. J., and Swerdlow, M. A.: Large duct epithelial hyperplasia and cancer of the breast. Arch. Surg., 97:592-594,1968. 15. Maier, W. P., Rosemond, G. P., Harasym, E. L., Jr., AI-Saleem, T. I., Tassoni, E. M., and Schorr, S. S.: Paget's disease in the female breast. Surg. Gynec. Obstet., 129:1253-1263, 1969. 16. McDivitt, R. W., Hatter, R. V. P., Foote, F. W., and Stewart, F. W.: In situ lobular carcinoma. J.A.M.A., 201 :96-100,1967. 17. McDivitt, R. W., Stewart, F. W., and Berg, J. W.: Tumors of the breast. In Atlas of Tumor Pathology, 2nd series, Fasc. 2. Washington, D.C., Armed Forces Institute of Pathology, 1968. 18. McLaughlin, C. W., Jr., Shenken, J. R., and Tamisier, J. X.: A study of precancerous epithelial hyperplasia and noninvasive papillary carcinoma of the breast. Ann. Surg., 153:735-744,1961. 19. Moertel, C. G., Dockerty, M. B., and Baggenstoss, A. H.: Multiple primary malignant neoplasms. III. Tumors of multicentric origin. Cancer, 14:238-244, 1961.
182 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
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Muir, R.: The evaluation of carcinoma of the mammal. J. Path. Bact., 52:155-172,1941. Newman, W.: In situ lobular carcinoma of the breast. Ann. Surg., 157:591-599, 1963. Newman, W.: Lobular carcinoma of the female breast. Ann. Surg., 164:305-314, 1966. Pellettiere, E. V.: Personal communication. Ross, W. L.: The magnitude of the breast carcinoma problem in the U.S.A. Cancer, 24:1106-1108,1969. Schwartz, A. M., and Siegelman, S. S.: Nonpalpable carcinoma in fibrocystic disease of the breast. Surg. Gynec. Obstet., 126:94-98,1968. Snyder, R. E.: Mammography and lobular carcinoma in situ. Surg. Gynec. Obstet., 122:255-260,1966. Stein, A. A.: Carcinoma in situ of the breast. A review. Pathology Annual, 1967, pp. 47-75. Steinhoff, N. G., and Black, W. C.: Florid cystic disease preceding mammary carcinoma. Ann. Surg., 171 :501-508,1970. Stewart, F. W.: Tumors of the breast. In Atlas of Tumor Pathology, Section IX, Fasc. 34. Washington, D.C., Armed Forces Institute of Pathology, 1950. Swerdlow, M., and Humphery, L. J.: Fibrocystic disease and carcinoma of the breast. Arch. Surg., 87:457-463,1963. Tellum, M., Shane, J. J., and Imbriglia, J. E.: Breast carcinoma in postmenopausal years. Surg. Gynec. Obstet., 120:17-24, 1965. Toker, C.: Some observations on Paget's disease in the nipple. Cancer, 14:653-672, 1961. Urban, J. A.: Bilaterality of cancer of the breast. Cancer, 20:1867-1879,1967. Urban, J. A.: Radical mastectomy in continuity with en bloc resection of the internal mammary lymph node chain. Cancer, 5:992-998, 1952. Warner, N. E.: Lobular carcinoma of the breast. Cancer, 23:840-846,1967. Warren, S.: The relation of "chronic mastitis" to carcinoma of the breast. Surg. Gynec. Obstet., 71 :257,1940.
Rush-Presbyterian-St. Luke's Medical Center 1753 West Congress Parkway Chicago, Illinois 60612
Carcinoma In Situ of the Breast
William D. Shorey, MD.*
In 1971, more than 65,000 new cases of carcinoma of the breast will be diagnosed. 3,24 Of that number, about the same percentage of patients will die of cancer of the breast as in the time of Halsted. 2 The paradox that 85 to 90 per cent of tumors are found by the patients themselves, and then only with an average size of 5 cm., must be contrasted with the availability of the organ sturcture for examination and inspection. From studies done by numerous authors!. 6, 9, 18,27 it is apparent that tumors of the breast, as in other related hormonally controlled structures such as the cervix,4 do not develop in a short period of time, but rather over a period of many years to decades. It is therefore significant to consider the problem of those changes which occur in the breast which may be considered as "in situ" carcinomas and their relationship to the possible progression to invasive carcinomas or separate, and possibly cellularly different, carcinomas. In the past decade the combination of mammography with biopsy of lesions suspicious either radiographically or on physical examination has given us a greater insight as to the frequency and significance of this condition. The types of "in situ" carcinomas to be discussed are those as outlined by Stewart.29 Lobular Carcinoma In Situ Since the original description of lobular carcinoma in situ by Foote and Stewart5 in 1941, numerous reports of this form of cancer of the breast have been published. 6 , 11.12. 17.35 In the past 2 years, the incidence of lobular carcinoma in situ in our hospital has been 8 per cent. 23 This compares with a incidence of 10.2 per cent reported by Newman21 in a series of 1436 primary carcinomas of the breast. The average age at the time of initial diagnosis was from 44 to 48.3 years, with a range of 29 to 83 years. 22 As pointed out by Foote and Stewart, this diagnosis of lobular carcinoma, either in situ or invasive, is a pathologist's diagnosis. 5 The diagnosis should not be made on a frozen section, but rather on permanent sections of suspicious areas. Clinically the lesion is of small size and *Associate Professor of Surgery. University of Illinois College of MediCine; Attending Surgeon, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois Surgical Clinics of North America- Vol. 51, No.1, February 1971
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is found in biopsies in which the primary pathology is that of "chronic cystic mastitis." Lobular carcinoma is multifocal and secondary foci will be found in the majority (70 per cent) of breasts subject to mastectomy of the ipsilateral breastY The propensity for this condition to occur simultaneously in both breasts has been recognized for many year~. Newman has shown that random biopsies of the upper outer quadrant of the contralateral breast at the time of diagnosis of the primary lesion will reveal bilateral disease in 23 per cent. 22 McDivitt reports an incidence greater than 30 per cent.17 Urban33 reports a somewhat higher figure of 59 per cent. It has been shown that lobular carcinoma in situ, if treated only by local excisional biopsy, will develop into infiltrating carcinoma in a significantly high percentage of cases. McDivitt et aP6 report that the incidence of ipsilateral carcinoma at 5 years is 8 per cent, but rises to 35 per cent at 20 years. For the contralateral breast, the incidence is 10 per cent in 10 years, increasing to 25 per cent in 20 years. In recent years the diagnosis of lobular carcinoma in situ has been made prior to biopsy in an increasing number of cases. Mammography, as shown by Snyder 6 and Hatter,12 may point out suspicious areas of calcification in otherwise normal breasts, or in relation to areas more suggestive of chronic cystic mastitis. The cooperation of radiologist, pathologist, and surgeon will insure that the proper area or areas for biopsy are successfully removed. Lobular carcinoma occurs in situ in 40 to 50 per cent of all cases of lobular carcinoma. If, on permanent section, the lesion is shown to be an infiltrating process, radical mastectomy should be performed. 29 Theoretically, if the lesion is found to be lobular carcinoma in situ, simple mastectomy should and has produced 100 per cent control of the disease. 17 However, a review of sections taken from a breast following simple mastectomy has frequently shown areas of invasion in sites other than that removed at the first biopsy. It is therefore the consensus of most authors l7 . 22 that simple mastectomy should be combined with a lower axillary dissection. If, at the table, the axillary dissection should appear or prove to show lymph node involvement, the procedure should be converted into a radical mastectomy. . The prognosis for survival of truly lobular carcinoma in situ with such a simple mastectomy is 100 per cent. For lobular carcinoma with invasion without positive nodes, Newman reports 31 of 36 patients alive at 5 years, and for those with positive nodes, 18 of 37 alive at 5 years. McDivitt reports a 42 per cent 10-year survival rate in his patients with positive lymphatic involvement. Because of the bilaterality of this condition, a biopsy selected by mammograph, or, if no radiographic abnormality exists, a random biopsy of the upper outer quadrant, should be carried out following or concurrently with the treatment of the primary breast. A negative biopsy alone should be the basis for a long and close follow-up of these patients, combined with periodic mammographic examination. Intraductal Carcinoma In Situ This has been recognized as a premalignant lesion since the work of Foote and Stewart in 1945.6 The diagnosis has been universally
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recognized by the criterion first laid down by Foote and Stewart and confirmed by other pathologists. L 10, 19,27 The treatment of this condition is based on the fact that it is extremely difficult to be absolutely certain, even on multiple sections, that no evidence of invasion exists beyond the basement membrane. Gallagar and Martin9 report two cases of intraductal carcinoma in situ with metastasis to axillary lymph nodes in which multiple sections of whole breast mounts at 0.5 mm. thickness failed to show the areas of invasion. It is obvious that the diagnosis of intraductal carcinoma, whether in situ or invasive, cannot be made on frozen section unless an obvious area of invasion can be suspected macroscopically and confirmed by frozen section. The usual course of events will be that the diagnosis is suspected on frozen section and confirmed 24 hours later by permanent sections-either as in situ or invasive carcinoma. If invasive, radical mastectomy is the procedure of choice. If in situ, simple or subcutaneous mastectomy should suffice to control the disease process. Biopsy of the contralateral breast should also be done: since this type of breast lesion is bilateral in 32 to 40 per cent of the cases. 33 However, lacking the facilities for semi-serial sections, a focus of infiltrating carcinoma is most difficult to exclude. In case of any doubt whatsoever, radical mastectomy is the procedure of choice and will give the highest percentage of longer than 10 year survival free of disease. 2o A variance of intraductal carcinoma is Paget's disease. This is defined by Muir2° as an intraductal carcinoma of the large ducts at or just beneath the nipple. It constitutes 1 to 4 per cent of all carcinomas of the breast. This disease entity is first recognized by an eczematoid thickening of the nipple, with or without retraction. In the earlier stages and in its in situ form, no mass is generally palpable. Mammography is of little value in diagnosis, which can only be made by biopsy. If a mass beneath or in the nipple is present to palpation, local invasion must be assumed and the lesion treated with a radical mastectomy or simple mastectomy with axillary dissection following biopsy. Those lesions truly in situ, with no evidence of invasion beyond the basement membrane, may be adequately treated in the postmenopausal patient by simple mastectomy. The survival of patients with in situ lesions is reported as 96 per cent in a series of 27 patients treated by simple mastectomy. Among postmenopausal patients with lymph node involvement, 7 of 23 died in 5 years. In premenopausal patients, all with positive nodes died in the same period, and five of nine died when the nodes were not involved with tumor.22 It must be emphasized that the prognosis of Paget's disease is not to be taken lightly. Toker 2 has shown by 1050 serial sections of one case of Paget's disease that the cells which caused the invasion of the nipple arose in a carcinoma 3 cm. in depth from the nipple. This occurred through intra-epithelial spread by permeation in the wall of the duct. It is difficult to conceive of this type of involvement as other than invasively malignant. In a series reported by McDivitt et alP a mass was clinically present in the breast at or adjacent to the diseased nipple in only 24 of 38 cases in which it was later proven pathologically that a mass was present. Therefore, I feel that an "in situ" diagnosis of Paget's disease should be
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confirmed by permanent sections prior to treatment by simple mastectomy. All others should be treated with a radical dissection. If there are positive axillary nodes, an extended radical mastectomy as described by Urban34 or radiation to the internal mammary chain should be considered for complete therapy of this lesion. Chronic Cystic Mastitis Should chronic cystic mastitis be considered as a premalignant, pre-in situ carcinoma? Foote and Stewart point out that the term chronic cystic mastitis is too broad, includes too many morphologic patterns, and that any point may be made by proper selection of criteria. However, since the work of Warren,37 a growing number of authors have pointed out the coexistence of forms of specific changes in the breast, which are commonly diagnosed "chronic cystic mastitis," with either in situ or invasive carcinoma. Gallagail has shown in 100 per cent of 60 breasts with primary carcinomas that there are concomitant and separate changes in the ductal epithelium. These changes range from simple hyperplasia, to hyperplasia with atypical cells, to in situ carcinoma. This is, in general, a diffuse process in the breast. Tellum31 reports that his series shows 3 to 5 times the normal incidence of carcinoma in women who have had chronic cystic mastitis. In a series of 90 women over 60 years of age, 54 had intraductal carcinoma adjacent to or removed from the primary carcinoma. In 24 of this group there was marked ductal hyperplasia. Similar findings are reported by Steinhoff and Black,28 who point out that lobular and papillomatous changes seem to be the ones most commonly associated with primary carcinoma. Both Stein 27 and Gallagar 9 suggest that there is a probability that breast tissue may pass through a hyperplastic stage with atypism on the path to an in situ or invasive carcinoma. They stress, however, that this progression is a nonobligate change. Changes from atypism in ductal or lobular structures to normal have frequently been recorded. The mechanism of this is unknown. These epithelial changes may take the form of papillomatous growths, which have been categorized as intraductal papilloma, intraductal papillomatosis, or epithelial hyperplasia with or without atypism. The relationships of these changes to carcinoma have been extensively discussed by many authors. 1, 6, 9,10,11,13,14, 18, 19,23 In my opinion it is probably accurate to state that women who have such changes constitute, from a pathological point of view, a group which has a higher risk of developing an in situ cancer or an invasive lesion. Further, if a patient should have two or more biopsies of suspicious lesions, the degree of dysplasia of the ductal elements should be carefully recorded. If there are changes of a progressive nature toward atypism, the risk of the patient developing a cancer must be considered as increasing. At the Presbyterian-St. Luke's Hospital the form shown in Figure 1 has been adopted to record certain types of specific cellular abnormalities in all breast biopsies or mastectomy specimens. This is designed to
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BREAST PATHOLOGY REPORT Specimen from: Right Breast 1 Left Breast 2 Date of operation: I I Mo I Day I Yr CODE
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DIAGNOSIS (Circle applicable code numbers below)
A. FIBROCYSTIC DISEASE
1110 Sclerosis, inflammation, cysts, stasis, and ductal ectasia 1210 Hyperplasia of duct epithelium-slight 1220 Hyperplasia of duct epithelium-moderate 1230 Hyperplasia of duct epithelium-severe 1240 Hyperplasia of duct epithelium-atypical 1310 Lobular hyperplasia-slight 1320 Lobular hyperplasia-moderate 1330 Lobular hyperplasia-severe 1340 Lobular hyperplasia-atypical 1411 Duct papillomatosis - solitary, typical 1412 Duct papillomatosis-solitary, atypical 1421 Duct papillomatosis-multiple, typical 1422 Duct papillomatosis-multiple, atypical 1510 Sclerosing adenosis-focal 1520 Sclerosing adenosis-diffuse 1610 Blunt duct adenosis 1710 Apocrine metaplasia 1810 Fibroadenomatous change 1910 Fat necrosis (nontraumatic) B. MALIGNANT NEOPLASMS 2111 NOninfiltrating, papillary, solitary 2112 Noninfiltrating, papillary, multiple 2121 Noninfiltrating, ductal 2131 Noninfiltrating, lobular 2211 Infiltrating, papillary, solitary 2212 Infiltrating, papillary, multiple 2221 Infiltrating, ductal 2231 Infiltrating, comedo carcinoma (with central necrosis) 2241 Infiltrating, medullary 2251 Infiltrating, mucinous 2261 Infiltrating, lobular 2271 Infiltrating, epidermoid 3110 3120 3210 3310 3410
Fibroadenoma, benign Fibroadenoma, malignant Mesodermal (e.g., sarcoma) Reticular (e.g., lymphoma) Epithelial (e.g., sweat gland, adenoid cystic)
C. LYMPH NODES Total number Number positive _ _ __ Figure 1
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be placed in a computer for easy recall to facilitate the review of an individual patient's progression as well as for statistical study. In all patients with a suspicious lesion, generous excisional biopsy is recommended. This is not only to insure the complete removal of the primary pathology but also to give to the surgeon and pathologist an understanding of the surrounding "normal" breast tissue left behind. For those cases in which an intraductal papilloma is suggested by a localized serous or bloody discharge, a quadrant excision is the procedure of choice. 1 The suspicion of a papillomatous process, either single or multiple, is a contraindication to frozen-s~ction diagnosis. Permanent sections will afford much better definition on such specimens and the chance of losing the papilloma will be avoided. If the biopsy should reveal significant cellular atypism of the ductal cells, either in the form of a single papilloma or multiple papillomatolls foci, the patient as a whole should be evaluated. The family history of carcinoma, age, and number of previous biopsies must be considered in relation to the patient's emotional status. Though it must be emphasized, as pointed out by Foote and Stewart,S that there must be many more studies of a prospective nature to prove that there is a causal relationship between ductal atypism and cancer, the risk of malignancy is always present and may well be increased. It may, in individual cases, seem wise to suggest bilateral simple mastectomy in these selected cases. With the development of more aesthetically satisfactory breast prostheses, subcutaneous mastectomies are being utilized, followed at a later date by a reconstructive procedure. It must be emphasized that meticulous care must be taken to remove the entire breast structures in either procedure, especially the "tail of Spence." For all patients not treated by primary mastectomy, it is our practice to follow them at frequent intervals, especially those who have significant cellular atypia in,their lobular or ductal structures. A team of surgeon, pathologist, and radiologist must work together to locate and remove areas of suspicious nature, suggested either by palpation or mammography. It is hoped that through this effort,- carried out on a continuing basis, a higher proportion of in situ lesions may be identified and, through proper treatment, may result in a decrease in the mortality statistics of this disease.
SUMMARY . Lobular carcinoma has few physical signs. It is a diagnosis made pathologically on permanent section. Recently mammography has proven helpful in suggesting its presence. If it occurs in situ, it should be removed by a mastectomy with low axillary dissection. If it is invasive, on biopsy or at the time of axillary dissection, radical dissection with or without postoperative irradiation therapy has given the best results. Intraductal carcinoma in situ is again a pathologist's diagnosis. The possibility of it being invasive is higher than in lobular carcinoma.
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Treatment is therefore more often of a raqical nature. Paget's disease may be considered a variant of this condition. The changes of ductal epithelium toward atypism, seen only too often in otherwise typical "chronic mastitis," may be a pre-pre-in situ lesion. These changes are reversible in many patients. A team approach of surgeon, diagnostic radiologist, and pathologist affords the basis of a rational approach to the proper treatment of these patients on an individual basis. The importance of a prolonged prospective study of this condition is emphasized.
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ACKNOWLEDGMENT
I wish to express my gratitude to Dr. Edmund Pellettiere for the use of his unpublished data.
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REFERENCES 1. Buhl-Jorgensen, s. E., et al.: Cancer risk in intraductal papilloma and papillomatosis. Surg. Gynec. Obstet., 127:1307-1312, 1968. 2. Cutter, S. J., and Connelly, R. R.: Mammary cancer trends. Cancer, 23:767-771,1969. 3. Dunn, J. E., Jr.: Epidemiology and possible identification of high risk groups that could develop cancer of the breast. Cancer, 23: 775-780, 1969. . 4. Fluhmann, C. F.: The Cervix Uteri and Its Diseases. Philadelphia, W. B. Saunders Co., 1961. 5. Foote, F. W., and Stewart, F. W.: Lobular carcinoma in situ. Amer. J. Path., 17:491-496, 1941. 6. Foote, F. W., and Stewart, F. W.: Comparative studies of cancerous versus noncancerous breasts. II. Rate of so-called chronic cystic mastitis in mammary carcinogenesis. Ann. Surg., 121 :197-221,1945. 7. Frantz, V. K., Pickren, J. W., Melcher, G. W., and Auchencloss, H., Jr.: Incidence of chronic cystic mastitis in so-called normal breasts; study based on 225 post mortem examinations. Cancer, 4:762,1951. 8. Funderburk, W. W., and Syphax, B.: Evaluation of nipple discharge. Cancer, 24:12901296,1969. 9. Gallagar, H., and Martin, J. E.: Early phases in the development of breast cancer. Cancer, 24:1170-1178,1969 . 10. Gillis, D. A., Dockerty, M. B., and Clagett, O. T.: Preinvasive intraductal carcinoma of breast. Surg. Gynec. Obstet., 110:555-559, 1960. 11. Haagenson, C. D.: Lobular carcinoma of the breast. Clin. Obstet. Gynec., 5:1093-1101, 1962. 12. Hatter, R. V. P., Snyder, R. E., Lucas, J. C., Foote, F. W., and Farrow, J. H.: Clinical and pathological correlations with mammographic findings in lobular carcinoma in situ. Cancer, 23:826-839,1969. 13. Humphery, L. J., and Swerdlow, M. A.: Relationship of benign breast disease to carcinoma ofthe breast. Surgery, 52:841-846,1962. 14. Humphery, L. J., and Swerdlow, M. A.: Large duct epithelial hyperplasia and cancer of the breast. Arch. Surg., 97:592-594,1968. 15. Maier, W. P., Rosemond, G. P., Harasym, E. L., Jr., AI-Saleem, T. I., Tassoni, E. M., and Schorr, S. S.: Paget's disease in the female breast. Surg. Gynec. Obstet., 129:1253-1263, 1969. 16. McDivitt, R. W., Hatter, R. V. P., Foote, F. W., and Stewart, F. W.: In situ lobular carcinoma. J.A.M.A., 201 :96-100,1967. 17. McDivitt, R. W., Stewart, F. W., and Berg, J. W.: Tumors of the breast. In Atlas of Tumor Pathology, 2nd series, Fasc. 2. Washington, D.C., Armed Forces Institute of Pathology, 1968. 18. McLaughlin, C. W., Jr., Shenken, J. R., and Tamisier, J. X.: A study of precancerous epithelial hyperplasia and noninvasive papillary carcinoma of the breast. Ann. Surg., 153:735-744,1961. 19. Moertel, C. G., Dockerty, M. B., and Baggenstoss, A. H.: Multiple primary malignant neoplasms. III. Tumors of multicentric origin. Cancer, 14:238-244, 1961.
182 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
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Muir, R.: The evaluation of carcinoma of the mammal. J. Path. Bact., 52:155-172,1941. Newman, W.: In situ lobular carcinoma of the breast. Ann. Surg., 157:591-599, 1963. Newman, W.: Lobular carcinoma of the female breast. Ann. Surg., 164:305-314, 1966. Pellettiere, E. V.: Personal communication. Ross, W. L.: The magnitude of the breast carcinoma problem in the U.S.A. Cancer, 24:1106-1108,1969. Schwartz, A. M., and Siegelman, S. S.: Nonpalpable carcinoma in fibrocystic disease of the breast. Surg. Gynec. Obstet., 126:94-98,1968. Snyder, R. E.: Mammography and lobular carcinoma in situ. Surg. Gynec. Obstet., 122:255-260,1966. Stein, A. A.: Carcinoma in situ of the breast. A review. Pathology Annual, 1967, pp. 47-75. Steinhoff, N. G., and Black, W. C.: Florid cystic disease preceding mammary carcinoma. Ann. Surg., 171 :501-508,1970. Stewart, F. W.: Tumors of the breast. In Atlas of Tumor Pathology, Section IX, Fasc. 34. Washington, D.C., Armed Forces Institute of Pathology, 1950. Swerdlow, M., and Humphery, L. J.: Fibrocystic disease and carcinoma of the breast. Arch. Surg., 87:457-463,1963. Tellum, M., Shane, J. J., and Imbriglia, J. E.: Breast carcinoma in postmenopausal years. Surg. Gynec. Obstet., 120:17-24, 1965. Toker, C.: Some observations on Paget's disease in the nipple. Cancer, 14:653-672, 1961. Urban, J. A.: Bilaterality of cancer of the breast. Cancer, 20:1867-1879,1967. Urban, J. A.: Radical mastectomy in continuity with en bloc resection of the internal mammary lymph node chain. Cancer, 5:992-998, 1952. Warner, N. E.: Lobular carcinoma of the breast. Cancer, 23:840-846,1967. Warren, S.: The relation of "chronic mastitis" to carcinoma of the breast. Surg. Gynec. Obstet., 71 :257,1940.
Rush-Presbyterian-St. Luke's Medical Center 1753 West Congress Parkway Chicago, Illinois 60612