| Abstract|| |
Background: Columnar cell lesions (CCLs) with or without atypia frequently coexist with invasive or in situ breast carcinomas. In this study, 39 mastectomy specimens containing CCLs coexisting with invasive carcinomas were retrospectively analyzed for cellular characteristics and structural pattern of CCL neighboring the tumor. Materials and Methods: The expression of estrogen receptor (ER), progesterone receptor (PR), and p53 antibodies in CCL and coexisting invasive tumors, type of invasive tumor, histopathologic grade, and presence of atypia in CCL have been studied. Results: Sixteen (41%) of all CCLs were with atypia, whereas 23 (59%) of them were without atypia. No correlations were found between the presence of CCLs with atypia and either the morphologic type of carcinoma or histopathologic grade of the tumors. Presence of atypia in the CCL was not correlated with the expression of p53 in the invasive tumors. CCLs without atypia dominated in Grade III tumors. The percentages of CCLs without atypia were also higher in both ER (−) and PR (−) tumors. Conclusions: CCL with atypia is generally considered to be a precursor of invasive carcinoma; however, in our study, CCLs without atypia more frequently coexisted with breast carcinoma.
Keywords: Breast, columnar cell lesion, invasive carcinoma
|How to cite this article:|
Demiralay E, Demirhan B, Koçbiyik A, Sar A, Altaca G. Immunohistochemical and morphologic findings in columnar cell lesions of the breast. Indian J Pathol Microbiol 2011;54:335-8
|How to cite this URL:|
Demiralay E, Demirhan B, Koçbiyik A, Sar A, Altaca G. Immunohistochemical and morphologic findings in columnar cell lesions of the breast. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Jul 12];54:335-8. Available from: http://www.ijpmonline.org/text.asp?2011/54/2/335/81630
| Introduction|| |
The development of breast cancer is now believed to be a complex multistep process originating in terminal duct lobular units (TDLUs) and progressing toward invasive cancer. ,,,,,,,,,,,,,, Recent attention has focused on a group of TDLU lesions called columnar cell lesions (CCLs).  CCLs with or without atypia frequently coexist with invasive or in situ carcinomas. ,,, Observations support the hypothesis that these lesions are low-grade precursors of in situ and invasive neoplastic lesions of the breast. ,,,,,,
In this study we aimed to analyze the morphologic and immunophenotypic features of invasive breast carcinoma and coexisting CCLs.
| Materials and Methods|| |
Thirty-nine mastectomy specimens containing CCLs coexisting with invasive carcinomas were retrospectively analyzed for cellular characteristics and structural pattern of CCLs neighboring the tumor. Hematoxylin and eosin-stained sections of paraffin-embedded blocks were studied by routine light microscopy for histopathologic type, grade of invasive tumor, and existence of atypia in the neighboring CCLs. We measured the major axis of lesion nests with an ocular micrometer in each case and recorded. The total diameter of all lesions was recorded in case the lesions were scattered.
Immunohistochemical analyses were performed on formalin-fixed paraffin-embedded tissue sections using of the avidin-biotin peroxidase complex method. Positive controls used were sections of breast carcinoma known to be positive for each of the other markers.
Immunohistochemical staining was performed with estrogen receptor (ER), progesterone receptor (PR), and with p53 primary antibodies and the staining patterns were scored. For ER, PR, and p53, staining was expressed as negative (-) or positive (+). Statistical analyses have been performed by SPSS (SPSS inc. Chicago, USA) V11.5.
| Results|| |
Features of coexisting CCL according to the histopathologic types of carcinoma are shown in [Table 1]. Coexisting CCLs were with atypia in 41% and without atypia in 59% [Figure 1] and [Figure 2]. The mean size of the CCLs was 3,053 mm (range: 0.4-8 mm).
|Figure 1: Columnar cell lesion. The acini are lined by a single layer of columnar epithelial cells and the cells show apical cytoplasmic snouts. (Hematoxylin and eosin, ×400)|
Click here to view
|Figure 2: Columnar cell lesions (CCLs). (a and b) These dilate acini show cellular stratification of more than two cell layers (H and E, ×100). (c) The columnar cells show apical cytoplasmic snouts. The nuclei are ovoid to elongated with evenly distributed chromatin (H and E, ×400). (D) CCL with atypia. The lining cells show cytologic atypia characterized by enlarged, stratified, plump, ovoid nuclei with variably prominent nucleoli. (H and E, ×400)|
Click here to view
|Table 1: Features of coexisting CCL according to the histopathologic types of carcinoma|
Click here to view
Presence of atypia in the coexisting CCL according to the histopathologic grade of the tumors is shown in [Table 2]. The percentage of CCLs with or without atypia in Grade I and Grade II tumors were similar; however, CCLs without atypia dominated in Grade III tumors (5/6).
|Table 2: Presence of atypia in CCLs according to histopathologic grade of the tumor|
Click here to view
Eight of the invasive carcinomas were ER (-) in the total series. Among those, 6 of the CCLs were ER (+) [Figure 3]. In ER (-) invasive carcinomas, CCLs with and without atypia were present in 33% and 66%, respectively (P = 0.03) [Table 3].
|Figure 3: Expression of breast tumor markers in columnar cell lesions (CCLs). Positive progesterone receptor immunostaining in cells within atypic CCLs. (Progesterone receptor, ×400)|
Click here to view
All of the coexisting CCLs were PR (+) in PR (-) invasive tumors (n=4) and 3 of them were without atypia [Table 4]. The number of CCLs with and without atypia was similar in the PR (+) invasive tumors.
The p53 positivity rate in the invasive carcinomas was 33% (13 cases); among those, CCLs were with atypia in 6 (46%) and without atypia in 7 (54%). Among p53 negative invasive carcinomas, CCLs with and without atypia were present in 35% and 65%, respectively (P = 0.03). All the CCLs in the total series were p53 negative.
| Discussion|| |
CCLs are increasingly being encountered in breast biopsies because their associated microcalcifications are detected on mammographic screening. ,,,,,,,,,, CCLs have been variously referred to as columnar alteration of lobules, low-grade clinging carcinoma in situ, columnar alteration of lobules with prominent apical snouts and secretions, small ectatic ducts with ductal carcinoma in situ (DCIS), blunt duct adenosis, ductal intraepithelial neoplasia-flat type, unfolded lobules, and atypical cystic lobules. ,,,,,,,,
CCLs can be formed from a single or double layer of columnar cells that are regular in size and shape with relatively bland nuclear features arranged perpendicular to basement membrane. The nuclei are uniform; typically ovoid with finely dispersed chromatin with inconspicuous nucleoli. Mitoses are not generally seen. Secretions and calcifications are often present in the lumen and apical snouts are noted at the luminal aspect of the cells. ,,,,,,
CCLs of the breast are classified as with atypia and without atypia. CCL with atypia, which has been referred as clinging carcinoma of monomorphic type by some authors, is now described as ductal intraepithelial neoplasia 1a (DIN 1a) or flat epithelial atypia (FEA) in the recent WHO classification of breast tumors. 
Discrimination of these lesions from the clinically inconsiderable lesions becomes important because some part of the CCLs has correlation with atypical ductal hyperplasia, DCIS, and invasive carcinoma. Schnitt and Vincent-Saloman  have proposed a simplified terminology for CCLs of the breast, and have grouped these lesions into 4 basic categories: columnar cell change, columnar cell hyperplasia, columnar cell change with atypia, and columnar cell hyperplasia with atypia. The latter 2 entities alternatively are known as FEA. There is emerging evidence in recent years to suggest that FEA is of neoplastic origin or even the earliest morphologic manifestation of low-grade DCIS as well as a precursor of invasive tubular carcinoma. 
In the total series, CCLs with and without atypia were 41% and 59%, respectively. When the apocrine and metaplastic carcinomas (1 case each) are excluded, CCL with atypia was found to be highest in tubular carcinoma (60%), followed by mixed carcinoma (50%), invasive lobular carcinoma (43%), and invasive ductal carcinoma (33%). In the majority of reports, CCL with atypia is generally considered to be a precursor of invasive carcinoma; however, in our study, CCLs without atypia more frequently coexisted with breast carcinoma, and in 83% of Grade III tumors, CCLs without atypia were encountered. ,,,,,,,, No statistical significance was detected probably due to low numbers. The percentages of CCLs without atypia were also higher in both ER (-) and PR (-) tumors.
CCL is a nonobligate precursor for the development of invasive carcinoma. The lesions observed could be forme fruste that did not go on to develop into invasive ductal carcinoma.
Our findings are consistent with the previously demonstrated fact that all categories of CCLs show histologic, immunohistochemical, and molecular genetic features that are strikingly similar to those of in situ and invasive forms of breast cancer. , Large series and molecular and genetic studies are needed to define the exact role of CCL without atypia in breast cancer.
| References|| |
|1.||Abdel-Fatah TM, Powe DG, Hodi Z, Lee AH, Reis-Filha JS, Ellis IO. High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma. Am J Surg Pathol 2007;31:417-26. |
|2.||Dessauvagie BJ, Zhao W, Heel-Miller KA, Harvey J, Bentel JM. Characterization of columnar cell lesions of the breast: Immunophenotypic analysis of alteration of lobules with prominent apical snouts and secretions. Hum Pathol 2007;38:284-92. |
|3.||Fraser JL, Raza S, Chorny K, Connolly JL, Schnitt SJ. Columnar alteration with prominent apical snouts and secretions: A spectrum of changes frequently present in breast biopsies performed for microcalcifications. Am J Surg Pathol 1998;22:1521-7. |
|4.||Goldstein NS, O'Malley BA. Cancerization of small ectatic ducts of the breast by ductal carcinoma in situ cells with apocrin snouts: A lesion associated with tubular carcinoma. Am J Clin Pathol 1997;107:561-6. |
|5.||Ho BC-S, Tan PH. Flat epithelial atypia: Concepts and controversies of an intraductal lesion of the breast. Pathology 2005;37:105-11. |
|6.||Jacobs TW, Connally JL, Schnitt SJ. Nonmalignant lesions in breast core needle biopsies. Am J Surg Pathol 2002;26:1095-110. |
|7.||Kusama R, Fujimori M, Matsuyama I, Fu L, Ishii K, Hama Y, et al. Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: Assessment of ACD as a precancerous lesion. Pathol Int 2000;50:793-800. |
|8.||Martel M, Baron-Rodriguez P, Ocal IT, Dotto J, Tavassoli FA. Flat DIN 1 (flat epithelial atypia) on core needle biopsy: 63 cases identified retrospectively among 1,751 core biopsies performed over an 8-year period (1992-1999). Virchows Archiv 2007;451:883-91. |
|9.||Moinfar F. Flat ductal intraepithelial neoplasia of the breast. Arch Pathol Lab Med 2009;133:879-92. |
|10.||Moinfar F, Man YG, Bratthauer GL, Ratschek M, Tavassoli FA. Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type (clinging ductal carcinoma in situ). Cancer 2000;88:2072-81. |
|11.||Noel JC, Fayt I, Fernandez-Aguilar S, Buxant F, Boutemy R. Proliferating activity in columnar cell lesions of the breast. Virchows Arch 2006;449:617-21. |
|12.||Oyama T, Maluf H, Koerner F. Atypical cystic lobules: An early stage in formation of low-grade ductal carcinoma in situ. Virchows Arch 1999;435:413-21. |
|13.||Pinder SE, Reis-Filho JS. Histopathology: Non-operative breast pathology. J Clin Pathol 2007;60:1297-9. |
|14.||Schnitt JS. Flat epithelial atypia-classification, pathologic features and clinical significance. Breast Cancer Res 2003;5:263-8. |
|15.||Schnitt JS, Vincent-Saloman A. Columnar cell lesions of the breast. Adv Anat Pathol 2003;10:113-24. |
|16.||Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP, et al. Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol 2005;29:734-46. |
|17.||Tan PH, Ho BC, Selvarajan S, Yap WM, Hanby A. Pathological diagnosis of columnar cell lesions of the breast: Are there issues of reproducibility? J Clin Pathol 2005;58:705-9. |
|18.||Turashvili G, Hayes M, Gilks B, Watson P, Aparicio S. Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer? Virchows Arch 2008;452:589-98. |
|19.||Tavassoli FA, Devilee P, editors. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the breast and female genital tract. Lyon: IARC Press; 2003. p. 60-73. |
Baskent University Faculty of Medicine, Istanbul Hospital, Department of Pathology, Oymaci Sokak No:7, Altunizade, 34662, Istanbul
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]