Columnar Cell Lesions of the Breast: The Missing Link in Breast Cancer Progression?

Simpson, Peter T.; Gale, Theo; Reis‐Filho, Jorge S.; Jones, Chris; Parry, Suzanne; Sloane, J P; Hanby, Andrew M.; Pinder, Sarah; Lee, Andrew H.S.; Humphreys, S.; Ellis, Ian O.; Lakhani, Sunil R.

doi:10.1097/01.pas.0000157295.93914.3b

Cited by 248 publications

(247 citation statements)

References 26 publications

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“…Emerging evidence suggests that FEA may have an important role in neoplastic progression in the breast. 18,19 Whereas its ultimate role in breast tumorigenesis remains to be more clearly defined, available observational data have indicated that FEA often coexists with other lesions for which the clinical implications and management considerations are better understood such as ADH, DCIS, invasive carcinoma (particularly tubular carcinoma) and lobular neoplasia. 3,5,22,23 Therefore, the recognition of FEA is of importance for surgical pathologists because this serves as a 'red flag', particularly in core biopsies, for the possible presence of these other lesions.…”

Section: Discussionmentioning

confidence: 99%

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Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast

et al. 2006

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and 8 Addenbrooke's NHS Trust, Cambridge, UK Columnar cell lesions (CCLs) of the breast with low-grade/monomorphic-type cytologic atypia are being identified increasingly in biopsies performed owing to mammographic microcalcifications. The WHO Working Group on the Pathology and Genetics of Tumours of the Breast recently introduced the term 'flat epithelial atypia' (FEA) for these lesions. However, the ability of pathologists to reproducibly diagnose FEA and to distinguish it from CCLs without atypia has not been previously evaluated. Eight pathologists with an interest in breast pathology participated in a study to address this issue. The study reference pathologist provided the other seven study pathologists with a Powerpoint tutorial that included written criteria for, and representative images of, FEA and CCLs without atypia (ie, columnar cell change and columnar cell hyperplasia). Following review of the tutorial, the study pathologists examined images in Powerpoint format from 30 CCLs and were instructed to categorize each as either 'FEA' or 'not atypical'. Overall agreement among the eight pathologists was 91.8% (95% CI, 84.0-96.9%), and the multi-rater kappa value was 0.83 (95% CI, 0.67-0.94), which is within the 'excellent agreement' range. Agreement was slightly better for determining absence of FEA (92.8%: 95% CI, 84.1-97.4%), than for determining its presence (90.4%: 95% CI, 79.9-96.7%). We conclude that the diagnosis of FEA and its distinction from CCLs without atypia is highly reproducible with the use of available diagnostic criteria.

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Section: Discussionmentioning

confidence: 99%

“…7,14,[16][17][18][19] In fact, CCLs with cytologic atypia were initially recognized by Azzopardi as a form of DCIS that he designated 'clinging carcinoma'. 6,7,20 Subsequently, De Potter et al separated clinging carcinoma into two subtypes: clinging carcinoma with pleomorphic nuclei and clinging carcinoma with monomorphic nuclei.…”

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Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast

et al. 2006

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“…Micropapillary lesions seem to be an intermediate step between flat epithelial atypia and pure non-micropapillary atypical ductal hyperplasia with 43 and 61% of cancers at surgery. As stated by Simpson,27 there is a morphological and molecular continuum in the degree of proliferation and atypia, and all these lesions are a non-obligate, intermediary step in the development of low-grade carcinomas. Our results confirm this non-obligate continuum since when low-grade ductal carcinoma in situ or infiltrating carcinomas were present at excision, atypical ductal hyperplasia was present at microbiopsy in almost (34 out of 36) or all the cases (n ¼ 10), respectively.…”

Section: Interobserver Reproducibility In the Classification Of Epithmentioning

confidence: 93%

All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision

et al. 2011

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The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision. Factors associated with cancer at excision were Breast Imaging Reporting and Data System (BI-RADS5) lesions, large and/or multiple foci of mammographical calcifications, histological type, number, size and extension of atypical foci. Flat epithelial atypia alone was never associated with cancer at excision. BI-RADS5, atypical ductal hyperplasia (alone or predominant) and 43 foci of atypia were identified as independent pejorative factors. There was never any cancer at excision when these pejorative factors were absent (n ¼ 31). Presence of one (n ¼ 59), two (n ¼ 23) or three (n ¼ 14) factors was associated with cancer in 24, 15 and 13 cases with an odds ratio ¼ 5.8 (95% CI: 3-11.2) for each additional factor. We recommend that mammographical data and histological characteristics be taken into account in the decision-making process after diagnosis of atypia on microbiopsy. With experienced senologists and strict histological criteria, some patients could be spared surgery resulting in significant patient, financial and time advantages.

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“…[3][4][5][6][7] According to Schnitt and Vincent-Salomon, 1 columnar cell lesions have been grouped into the categories of columnar cell change and columnar cell hyperplasia without or with atypia. Other authors 8 have proposed a subcategorization of columnar cell lesions depending on the presence of architectural and/or cytological atypia. The unifying term 'flat epithelial atypia' has been proposed by the World Health Organization Working Group on the Pathology and Genetics of Tumors of the Breast 9 for columnar cell lesions with low-grade cytological atypia.…”

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confidence: 99%

“…11 On the other hand, it has been shown that the columnar cell lesions frequently coexist with and show the same genetic alterations of hormonedependent lesions, such as low-grade ductal carcinoma in situ (particularly, micropapillary and cribriform type), lobular intraepithelial neoplasia, and invasive tubular carcinoma. 8,12,13 All these data may be considered for postmenopausal women with a history of columnar cell lesions who are currently receiving or considering for hormone replacement therapy. Moreover, several experts in breast pathology underline that there is an urgent need for large, comprehensive studies describing more accurately the risk of finding malignant diseases after a diagnosis of columnar cell lesions on core biopsy specimens.…”

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confidence: 99%

Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations

et al. 2009

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Columnar cell lesions of the breast are increasingly recognized at mammography for their tendency to calcify. We studied 392 vacuum-assisted core biopsies performed solely for calcifications to evaluate the frequency of columnar cell lesions, their relationship with radiological risk, appearance of calcifications, and clinical data. Management and follow-up of columnar cell lesions without and with atypia (flat epithelial atypia) was analyzed. Cases with architectural atypia (cribriform spaces and/or micropapillae) were excluded from flat epithelial atypia. Calcifications were within the lumen of acini affected by columnar cell lesions in 137 out of 156 biopsies diagnosed with some columnar cell lesions. These represented 37% of vacuum-assisted core biopsies and 62% of low radiological risk (BI-RADS3) calcifications. High-risk (BI-RADS5) calcifications were never associated with columnar cell lesions. Age and menopausal status were comparable in columnar and in not-columnar cell lesions. Atypia was associated with long-term hormone replacement therapy in both lesions. Surgical biopsy was recommended for all cases with atypia. Flat epithelial atypia, as the only histological findings on vacuum-assisted core biopsies, was never associated with malignancy at surgery. In conclusion, we suggest that surgical excision is not mandatory when flat epithelial atypia is found as the most advanced lesion on vacuum-assisted core biopsy performed for low radiological risk calcifications, and that women should be advised of the possible hormone dependency of this entity. Modern Pathology ( Keywords: columnar cell lesions; flat epithelial lesion; calcifications Stereotactic vacuum-assisted core biopsy is currently used to diagnose indeterminate or suspicious breast calcifications that are histologically related to a spectrum of breast lesions encompassing ductal carcinomas in situ and preneoplastic and benign lesions. Often this type of calcification resides in so-called 'columnar cell lesions', 1 entities characterized by the presence of columnar epithelial cells lining the terminal duct lobular units that typically show flocculant or secretory material and microcalcifications in the lumen. The Breast Imaging Reporting and Data System (BI-RADS) 2 has standardized the description and management of findings identified on mammograms, thereby facilitating communication between radiologists and referring physicians. However, to our knowledge, there are no specific studies evaluating whether specific calcification descriptors are associate with columnar cell lesions.Columnar cell lesions have been described under a variety of names. [3][4][5][6][7] According to Schnitt and Vincent-Salomon, 1 columnar cell lesions have been grouped into the categories of columnar cell change and columnar cell hyperplasia without or with atypia. Other authors 8 have proposed a subcategorization of columnar cell lesions depending on the presence of architectural and/or cytological atypia. The unifying term 'flat epithelial atypia' has been proposed by ...

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Columnar Cell Lesions of the Breast: The Missing Link in Breast Cancer Progression?

Cited by 248 publications

References 26 publications

Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast

Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast

All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision

Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations

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