Annals of Clinical & Laboratory Science 33:23-31 (2003)
© 2003 Association of Clinical Scientists
Incidental Finding of Mammary Carcinoma in Lumpectomy Specimens
Ping Tang1,
Steven I. Hajdu1,
Charles C. Conte2 and
Dominic A. Filardi2
Departments of 1 Pathology and 2 Surgery, North Shore University Hospital, Manhasset, New York
Address correspondence to Steven I. Hajdu, M.D., Department of Pathology, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA; tel 516 562 4189; fax 516 562 4591.
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Abstract
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More and more breast lumpectomies are being performed due to mammographic screening, and both in situ and invasive breast carcinomas are being detected earlier and smaller in size. The objective of this study was to determine the presence of incidental microscopic breast carcinoma in mammography-guided lumpectomy specimens. A prospective study was carried out by processing in surgical pathology approximately 9,000 breast lumpectomy specimens during a 2.5-yr period so that the entire specimens were embedded for microscopic examination. Excluded from the study were cases with grossly or microscopically identified carcinomas greater than 10 mm2, and non-invasive carcinomas diagnosed in association with invasive carcinoma. Cases with multifocal carcinomas, prior diagnosis of breast cancer, or prior history of breast biopsy were also excluded. Carcinomas present in the same tissue blocks as the clinically suspected lesions such as palpable nodules, microcalcification, or other mammographic abnormalities were excluded as well. Fifty cases of incidental microscopic mammary carcinoma were found including 8 infiltrating ductal carcinomas (IDC), 2 infiltrating lobular carcinomas (ILC), 21 intraductal carcinomas (DCIS), and 19 lobular carcinomas in situ (LCIS). All of the lesions were solitary, located in indistinct loosely arranged fibrous and adipose stromal tissues, and the majority of them were near or at the inked excisional margins. Physicians who care for patients with breast cancer should be aware of the existence of these minute breast carcinomas that are often near or at the surgical margins. The significance of these microscopic findings for therapeutic strategy and prognosis should be determined by long-term follow-up.
(received 21 May 2001; accepted 25 August 2001)
Keywords: Microscopic breast carcinoma, ductal carcinoma in situ, lobular carcinoma in situ
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Introduction
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Breast carcinoma is one of the most common neoplasms of women and is a leading cause of cancer-related deaths worldwide. The incidence of breast carcinoma, especially small pre-invasive cancer, has increased during the past 10–20 yr, due to widespread mammographic screening. During the same period, the treatment of breast carcinomas has changed from mastectomy to breast conservation therapy (BCT) with or without radiotherapy (RT) and chemotherapy (CT) [1–4]. Recently, Nakamura et al [5] reported that margin width is the most important determinant for local recurrence of breast carcinoma. They showed that in patients treated with surgery only, the local recurrence rate was 6% if the width of the margin was >10 mm, and 73% if the margin width was <1 mm. In patients who received combination treatment by surgery and radiation, the local recurrence rate dropped to 3% if the margin width was >10 mm and to 35% if the margin width was <1 mm. These results suggest the possible presence of microscopic carcinomas that were left behind if treated with surgery alone.
The present paper reports a group of primary infiltrating and non-infiltrating breast carcinomas that were found incidentally on histopathologic examination of entirely embedded lumpectomy specimens. The carcinomas were solitary, <10 mm2 in diameter, and located away from the clinically or mammographically suspected lesions; many of the carcinomas were present at or near the inked lumpectomy margins.
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Materials and Methods
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During a period of 2.5 yr, approximately 9,000 breast lumpectomy specimens were examined in the Department of Pathology at North Shore University Hospital in such a way that the entire specimens were embedded for microscopic examination. All of the lumpectomy specimens arrived at the surgical pathology laboratory along with the clinical diagnosis, an x-ray film, and a comment from the radiologist regarding lesion localization if needed, such as for microcalcification and mass. Many specimens also had suture(s) to indicate the location of the lesion or margins. The size of the specimens was measured, the specimens were inked, and then serially sectioned. The cut surfaces were grossly examined carefully for clinically diagnosed lesions at the corresponding locations and for other incidental lesions. Gross descriptions of the location, size, color, and consistency of the lesions and the appearance of the surrounding tissue were also recorded. The clinically identified lesions and margins were submitted in designated tissue blocks and the remaining tissue was entirely submitted in undesignated tissue blocks.
To limit this study to incidental microscopic breast carcinomas that could only be found by histopathologic examination of the entirely embedded specimens, we excluded all microscopic carcinomas either at the prior biopsy site or with a prior diagnosis of breast carcinoma in the same breast. We also excluded carcinomas that were described grossly or were multifocal. All carcinomas >10 mm2, or carcinomas located in the same tissue block as clinically suspicious lesions (such as mammary nodules, fibroadenomas, microcalcification or fibrocystic changes) were excluded. Non-infiltrating breast carcinomas (DCIS and LCIS) in association with infiltrating carcinomas were also excluded. The pathologic slides of all cases that fulfilled these criteria were reviewed for two-dimensional tumor size, assessment of their relation to clinically suspected lesions, and measurement of the surgical margin width.
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Results
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Using specified criteria for the 9,000 lumpectomy cases, we identified 50 cases (0.6%) of incidental and microscopic mammary carcinomas, including 10 cases of IBC (8 cases of IDC, 2 cases of ILC), 21 cases of DCIS, and 19 cases of LCIS. The carcinomas were present in adipose and fibrous stromal tissues, at least 1–2 cm from the mammographically or clinically detected lesions, and were not detectable by gross visual examination or palpation at the time of dissection of the specimens.
Microscopic infiltrating breast carcinoma (IBC).
Ten cases of microscopic infiltrating breast carcinoma were identified (Table 1
), including 8 cases of infiltrating ductal carcinoma (IDC) and 2 cases of infiltrating lobular carcinoma (ILC); none of the 10 cases had prior biopsies or history of breast carcinoma. The mean age for IDC (52 yr) was >20 yr younger than that for ILC (75 yr). Among the 10 cases of IBC, lumpectomies were performed in 8 cases due to microcalcification and in 2 cases due to mass/nodules. In all 10 cases, the foci of the infiltrating carcinomas were in tissue blocks other than the ones in which the clinically suspected lesions (DCIS, LCIS, microcalcification, etc) were located. The size of the carcinomas ranged from 1 to 4 mm in greatest dimension, and the margin widths were <10 mm in all cases, including 2 cases with <1 mm margin. Of the 8 cases of IDC, 4 were associated with multifocal DCIS and the others were associated with fibrocystic changes. In all cases, multifocal microcalcifications were identified in non-invasive areas; none of the invasive carcinomas contained calcifications.
Surgical follow-ups were performed in 9 of the 10 IBC cases. One case (2x2 mm IDC with 5 mm margin) showed 2 positive sentinel lymph nodes, each with a 2 mm focus of carcinoma. One case (2x1 mm ILC with 5 mm margin) on re-excision showed multifocal LCIS and negative sentinel lymph node. The remaining cases had negative re-excision and negative sentinel lymph nodes or negative axillary lymph nodes (Table 1
).
Microscopic ductal carcinoma in situ (DCIS)
Twenty-one cases of microscopic DCIS (Table 2) were identified. The mean age of these patients was 61 yr. The lumpectomies were performed in 15 cases due to microcalcification and in 6 cases due to masses or nodules. In none of 21 cases were the DCIS in the same tissue blocks as the clinically or mammographically suspected lesions (eg, fibroadenoma, fibrocystic changes, microcalcification). The DCIS ranged from 1 to 6 mm in greatest dimension. The margin widths were 
1 mm in 10 cases, 2 to 5 mm in 9 cases, 8 mm in 1 case, and 10 mm in 1 case. Fibrocystic changes, the most commonly associated lesions with DCIS, were present in 16 cases, followed by LCIS in 4 cases and fibroadenoma in 1 case. Multifocal microcalcifications were identified in benign areas of all cases where calcification was detected mammographically, excepting 1 case with a solitary microcalcification. Among calcification-positive cases, microcalcification was also identified in association with DCIS in 6 cases in areas separate from the areas of microcalcification associated with benign lesions. Nineteen cases of DCIS were low-grade (cribriform, micropapillary, solid with or without central necrosis), and the other 2 cases were high-grade (comedo) DCIS.
For follow-up, wide re-excisions were performed in 11 cases, 8 of which showed benign breast tissue in entirely embedded re-excision specimens, 1 case had DCIS, 1 case had LCIS, and 1 case was found to have a 1 cm IDC 6 mo after prior lumpectomy. Mastectomies, elected by patients, were performed following the diagnosis of DCIS in 3 cases, 2 of which were bilateral. One case with a 3 mm lumpectomy margin had ipsilateral mastectomy 7 wk later and multiple foci of DCIS and LCIS were found on examination of 20 tissue blocks; there were 19 negative axillary lymph nodes. None of the areas with carcinoma were evident on gross examination of the mastectomy specimen. One case with a 3 mm surgical margin on the lumpectomy specimen had bilateral mastectomies 6 mo later at the request of the patient. We found ipsilateral DCIS (9 tissue blocks examined) and contralateral LCIS (8 tissue blocks examined). A case with 0.1 mm surgical margin had bilateral mastectomies 7 wk later and revealed ipsilateral DCIS (13 tissue blocks examined) and contralateral LCIS (8 tissue blocks examined) in the grossly negative mastectomy specimen. Five of the cases had negative medical follow-up; two were treated with chemo-, radio-, or hormonal therapy.
Microscopic lobular carcinoma in situ (LCIS)
Nineteen cases of LCIS (Table 3) were identified. The mean age was 55 yr. Among the 19 cases of LCIS, lumpectomies were performed in 11 cases due to microcalcification and in 8 due to masses or nodules. In all 19 cases, the foci of LCIS were located in tissue blocks other than the ones with the clinically suspected lesions (eg, fibroadenoma, fibrocystic changes, microcalcification). The LCIS ranged from 1 to 4 mm in greatest dimension and the margin widths were 5 mm in all cases including 7 cases with margins 1 mm. Fibrocystic changes were the most frequently associated lesions, present in all 19 cases; fibroadenomas were noted in 2 cases. Multifocal microcalcifications were identified in benign areas in all cases in which calcification was detected mammographically, except 1 case in which the calcification was solitary. Microcalcification was also identified in LCIS in 1 case. Surgical follow-up of one case (1x1 mm solitary LCIS with 2 mm margin on lumpectomy) on re-excision 2 yr later showed multifocal LCIS from 1 to 2 mm in greatest dimension.
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Discussion
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In this study, 50 cases of incidental microscopic invasive (IDC and ILC) and in situ (DCIS and LCIS) breast carcinomas were detected prospectively. All of these tumors had sizes <10 mm2 and were undetectable clinically, mammographically, or by gross examination of the surgical specimens. The carcinomas were identified only by histopathologic examination of the entirely embedded lumpectomy specimens. The result of this study raises the question whether current practice in surgical pathology, in which only tissues with a nodule, calcification, or other suspicious area on gross examination are processed for histopathological examination. Although the incidental breast carcinomas comprised only 0.6% of the lumpectomy specimens that were processed in toto for microscopic examination, the actual occurrence of such minute microscopic carcinomas may be much higher. Dooley [6] recently reported that unsuspected additional lesions (cancerous and pre-cancerous), located outside the anticipated areas in lumpectomy specimens, were found in 41% of 201 cases with routine operative breast endoscopy during lumpectomy. In the present study, none of 10 invasive and 40 non-invasive carcinomas was found by clinical and mammographical examinations. An additional concern is that all of the carcinomas were found in mammary tissues distant from areas that warranted surgical excision. Moreover, by routine blocking in surgical pathology, which would have generated ~50% fewer tissue blocks, most of the 50 carcinomas would have been undetected.
Ashikari et al [7] reported more than 30 yr ago that DCIS is occasionally associated with axillary lymph node metastases in the absence of pathologically documented invasive carcinoma. One can speculate that this phenomenon may, at least partly, be due to the presence of microscopic foci of invasive carcinoma that may be missed because of incomplete surgical excision or pathologic sampling of the surgically excised specimen. Our findings show that there are grossly undetectable microscopic invasive carcinomas with or without in situ component, which can be detected only by microscopic examination of the entirely excised tissue. Another explanation for axillary lymph node metastasis in association with intraductal comedo carcinoma was provided by us previously [8,9]. We reported ultrastructural evidence of invasive potential of high-grade comedo type DCIS. We found that comedo-type DCIS frequently has multiple ultrastructural defects in periductal areas, including variably expanded lateral space between adjacent myoepithelial cells, altered and fragmented basal lamina, and disorganized, and highly vascular periductal tenascin-rich matrix [8,9], all of which may facilitate early escape of intraductal tumor cells into adjacent mammary stroma.
We found metastatic carcinoma to sentinel lymph nodes in 1 case of IDC. Martin et al [10] reported that small invasive breast carcinomas, <5 mm, or 5 to10 mm, have significant risks of axillary involvement (ie, 12% and 15.7%, respectively). These results are supported by a recent study of Klauber-Demore et al [11]. It is unclear from these reports what is the optimal treatment for such minute, microscopic IBC, that are strictly pathologists’ findings.
It appears from our study that younger patients are frequently affected by this type of microscopic IBC. Three of 8 patients with microscopic IDC were less than 50 yr old. Michaelson et al [12] reported that 25% of the invasive carcinomas occur in patients <50 yr old. Thus, it is especially important to obtain adequate samples and to study with care the breast specimens from young women.
The recurrence rate, an important parameter for effectiveness of treatment of DCIS, has been shown to be closely correlated with the pathologic status of the margins [13], the histological grade, and the expression of cellular markers such as ER/PR, cerbB-2, bcl-2, p53, Ki67, and DNA diploidy [14]. Other factors such as periductal neovascularization, microcalcification, and periductal fibrosis may also play important roles [9,15]. The present study shows that microscopic breast carcinomas can remain undetected by routine surgical pathological processing. Optimal pathologic sampling may provide a pathological basis for more aggressive treatment, such as post-surgical radiation in cases with minimal surgical margins.
The surgical margin appears to be the most important factor that affects the outcome on re-excision [5]. Nearly half of the microscopic DCIS in this study had 1 mm surgical margins, which are technically positive margins according to some authors [16]. Furthermore, among the 21 microscopic DCIS, 5 cases with surgical follow-up showed residual tumor; 2 had a margin 1 mm and the other 3 had a margin 
2 mm, which is different from a recent report [12] that showed that DCIS with a margin >2 mm had no residual tumor on re-excision. We believe that ensuring adequate (eg 10 mm) tumor-free margin for microscopic DCIS is justified, but whether adjuvant radiation or chemotherapy should be carried out is beyond the scope of this study.
Although only one case of DCIS in our study has surgical follow-up with lymph node dissection, which was negative, Jimenez and Visscher [18] and Blauker-DeMore et al [11] have reported that either DCIS with microscopic invasion or DCIS with additional factors (eg, palpable mass, mammographic mass, histologically suspicious findings that are not diagnostic for microinvasion, multicentric disease, high nuclear grade, or necrosis) carry significant risk of axillary metastases.
The effect of nuclear-grade of DCIS on the rate of local recurrence is contraversial. In our study, only 2 of 21 cases of microscopic DCIS were classified as high-grade comedo type. Van Zee et al [19] reported that for DCIS, lower nuclear grade is associated with significantly lower rate of recurrence. However, Goldstein et al [20]showed that nuclear grade is not a good predictor of local recurrence. Instead, the volume of DCIS in the specimen and the volume of DCIS near the margin are important predictors for local recurrence [17,20].
We found microcalcifications in 6 of 21 cases of microscopic DCIS, suggesting that microcalcification can be a useful marker in detecting and locating microscopic DCIS by studying specimen radiographs at the time of pathologic sampling of the specimen. Homer [21] reported the usefulness of microcalcification in detecting nonpalpable breast carcinoma, demonstrating that microcalcification is confined to the tumor in 63% of cases.
The mean age of patients with microscopic DCIS was 61 yr, with 4 of 21 cases <50 yr old and 3 of 21 cases >70 yr old. Earlier studies have shown that the younger age of DCIS patients is associated with higher rate of local recurrence [19,20,22]. Therefore, just as is true in patients with infiltrating breast carcinoma, thorough pathologic examination and sampling of the specimen, particularly in younger patients, is the key to detecting minute carcinomas.
DCIS often recurs in the same breast or at the site of the original biopsy, so it is generally believed that DCIS is unicentric in most cases [23]. Our study supports this view by showing that the 2 cases of microscopic DCIS with bilateral mastectomy did identify additional DCIS ipsilaterally in both cases. This impression is further supported by studies showing that more aggressive treatment (ie, a combination of BCT and RT) dramatically decreases the rate of recurrent DCIS, compared to surgical treatment alone [24,25]. We concur with others [26–28] that DCIS is a precursor of infiltrating carcinoma. Thus, it is essential to detect and diagnose DCIS in a timely fashion, regardless of size.
In the 19 cases of incidental LCIS located away from the clinically suspected lesions, 8 of the lumpectomies were performed because of microcalcification, yet in only 1 of the 19 cases of microscopic LCIS actually associated with microcalcification. LCIS is regarded as a marker of increased risk for developing breast carcinoma rather than as a true non-invasive carcinoma [29]. However, LCIS, including microscopic LCIS, is associated with invasive lobular carcinoma in 5 to 16% of cases [30,31]. Although the implication for prognosis of incidental microscopic solitary LCIS, as identified in this study, remains to be determined, the existence of even microscopic LCIS should be noted and recorded.
In summary, we have identified 50 cases of microscopic mammary carcinomas, including 10 cases of infiltrating carcinomas, that were found incidentally on pathologic examination of totally sampled lumpectomy specimens. If only representative section had been submitted, 50% fewer tissue blocks would have been prepared for histological examination, and most, if not all, of these microscopic breast carcinomas would have been undetected. The rate of detecting this type of breast carcinomas is very low (0.6% of all breast cases examined) and evaluating the cost-effectiveness of sampling breast lumpectomy specimen in toto is not our intention. Our findings indicate that clinical and mammographical studies are insufficient to detect this type of lesion, as is gross pathological examination of the specimen. Our findings show the importance of pathologic sampling and microscopic examination of the entire surgical specimen. In view of the findings presented in this paper, our institution has adopted a permanent policy, with support of the administrative and professional staff, that all breast biopsies are submitted in toto for microscopic examination. Although the clinical signicance of these microscopic carcinomas can be determined only by long term follow-up of these patients, we feel it is a duty of pathologists to detect, diagnose, and report minute microscopic breast carcinomas of the kind reported in this study. Surgical oncologists, medical oncologists, radiation oncologists, and others who care for patients with mammary lesions should be aware of our findings and should find ways to assure that mammary carcinomas, even the smallest ones, are detected by pathologists in a timely fashion.
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References
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|---|
- Ernster VL, Barclay J, Kerlikowske K, Grady D, Henderson C. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 1996;275: 913–918.[Abstract/Free Full Text]
- Jacobson JA, Danforth DN, Cowan N, D’Angelo T, Steinberg SM, Pierce L, Lippman ME, Lichter AS, Glatstein E, Okunieff P, Ten-year results of a comparison of conservative surgery with mastectomy in the treatment of stage I and II breast cancer. N Eng J Med 1995;332:907–911.[Abstract/Free Full Text]
- Talamonti MS. Management of ductal carcinoma in situ. Semin Surg Oncol 1996;5:300–313.
- Amichetti A, Caffo O, Richetti A, Zini G, Rigon M, Antonello M, Arcicasa M, Coghetto F, Valdagni R, Maluta S, Di Marco A. Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy. Eur J Cancer 1997;33:1559–1565.
- Nakamura SK, Woo C, Sposto R, Waisman, JR, Silverstein MJ. Ductal carcinoma in situ (DCIS) of breast: margin width-the key predictor of local recurrence. SSO 55th Annual Cancer Symposium 2002, p 528.
- Dooley WC. Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol 2002;9:S9.
- Ashikari R, Hajdu SI, Robbins CF. Intraductal carcinoma of the breast. Cancer 1971;28:1182–1187.[Medline]
- Iskaros BF, Sison CP, Hajdu SI. Tenascin patterns of expression in duct carcinoma in situ of the breast. Ann Clin Lab Sci 2000;30:266–271.[Abstract]
- Tang P, Teichberg S, Roberts B, Hajdu SI. Ultra-structure of the periductal area of comedo carcinoma in situ of the breast. Ann Clin Lab Sci 2001;31:284–290.[Abstract/Free Full Text]
- Martin C, Cutuli B, Velten M. Predicative model of axillary lymph node involvement in women with small invasive breast carcinoma, axillary metastases in breast carcinoma. Cancer 2002;94:314–322.[Medline]
- Klauber-DeMore N, Tan LK, Liberman L, Kaptain S, Fey J, Borgen P, Heerdt A, Montgomery L, Paglia M, Petrek J, Cody HS, Van Zee KJ. Sentinel lymph node biopsy: Is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion? Ann Surg Oncol 2000;7:636–642.[Medline]
- Michaelson J, Satija S, Moore R, Weber G, Halpern E, Garland A, Puri D, Kopans DB. The pattern of breast cancer screening utilization and its consequences. Cancer 2002;94:37–43.[Medline]
- Gage I, Schnitt SJ, Nixon AJ, Silver B, Recht A, Troyan SL, Eberlein T, Love SM, Gelman R, Harris JR, Connolly JL. Pathologic margin involvement and the risk of recurrence in patients treated with breast-conversing therapy. Cancer 1996;78:1921–1928.[Medline]
- Ringberg A, Anagnostaki L, Anderson H, Idvall I, Ferno M. Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics. Eur J Cancer 2001;37:1514–1522.
- Claus EB, Chu P, Howe CL, Davison TL, Stern DF, Carter D, DiGiovanna MP, Pathobiologic findings in DCIS of the breast: morphologic features, angio-genesis, HER-2/neu and hormone receptors. Exp Mol Pathol 2001;70:303–316.[Medline]
- Poller DN. Pathology of ductal carcinoma in situ of the breast: current status. Eur J Surg Oncol 2001; 27:498–503.[Medline]
- Neuschatz AC, DiPetrillo T, Steinhoff M, Safaii H, Yunes M, Landa M, Chung M, Cady B, Wazer DE. The value of breast lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast. Cancer 2002; 94:1917–1924.[Medline]
- Jimenez RE, Visscher DW. Clinicopathologic analysis of microscopically invasive breast carcinoma. Hum Pathol 1998;29:1412–1419[Medline]
- Van Zee KJ, Liberman L, Samli B, Tran KN, McCormick B, Petrek JA, Rosen PP, Borgen PI. Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery: the effect of age. Cancer 1999;86:1757–1767.[Medline]
- Goldstein NS, Kestin L, Vicini F. Intraductal carcinoma of the breast, pathologic features associated with local recurrence in patients treated with breast-conserving therapy. Am J Sur Pathol 2000;24:1058–1067.
- Homer MJ, Safaii H, Smith TJ, Marchant DJ. The relationship of mammographic microcalcification to histologic malignancy: radiologic-pathologic correlation. Am J Roentgenol 1989;153:1187–1189.[Abstract/Free Full Text]
- Padmore RF, Fowble B, Hoffman J, Rosser C, Hanlon A, Patchefsky AS. Microinvasive breast carcinoma: clinicopathologic analysis of a single institution experience. Cancer 2000;88:1403–1409.[Medline]
- Lagios MD, Margolin FR, Westdahl PR, Rose MR. Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence. Cancer 1989;63:618–624.[Medline]
- Silverstein MJ, Lagios MD, Groshen S, Waisman JR, Lewinsky BS, Martino S, Gamagami P, Colburn WJ. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Eng J Med 1999;340:1455–1461.[Abstract/Free Full Text]
- Jha MK, Avlonitis VS, Griffith CDM, Lennard TWJ, Wilson RG, Mclean LM, Dawes PD, Shrimankar J. Aggressive local treatment for screen-detected DCIS results in very low rates of recurrence. Eur J Surg Oncol 2001;27:454–458.[Medline]
- Rosen PP, Braum DW Jr, Kinne DE. The clinical significance of pre-invasive breast carcinoma. Cancer 1980;46:919–925.[Medline]
- Eusebi V, Fendale E, Foschini MP, Micheli A, Conti A, Riva C, DiPalma S, Rilke F. Long-term follow-up of in situ carcinoma of the breast. Semin Diagn Pathol 1994;11:223–235.[Medline]
- Maluf H, Koerner F. Lobular carcinoma in situ and infiltrating ductal carcinoma: frequent presence of DCIS as a precursor lesion. Int J Surg Pathol 2001;9: 127–131.[Abstract/Free Full Text]
- Frykberg ER. Lobular carcinoma in situ of the breast. Breast J 1999;5:296–302.[Medline]
- Tulusan AH, Egger H, Schneider ML, Willgeroth F. A contribution to the natural history of breast cancer: IV. Lobular carcinoma in situ and its relation to breast cancer. Arch Gynecol 1982;231:219–226.[Medline]
- Hutter RVP. The management of patients with lobular carcinoma in situ of the breast. Cancer 1984;53:798–802.[Medline]
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Abstract
Introduction
