Analysis of Clinical and Pathologic Factors of Pure, Flat Epithelial Atypia on Core Needle Biopsy to Aid in the Decision of Excision or Observation.

BACKGROUND: The optimal treatment of flat epithelial atypia (FEA) found on breast core needle biopsy (CNB) is controversial. We performed a retrospective review of our institutional experience with FEA to determine if excisional biopsy may be deferred. METHODS: Surgical records from 2009 to 2012 were reviewed for FEA diagnosis. After exclusion for concomitant lesions, CNBs of pure FEA were classified using a previously agreed upon descriptor of "focal" versus "prominent". Data was analyzed with the Fisher's Exact and Student-t test as appropriate. RESULTS: Of 71 CNBs evaluated, pure FEA was identified on 27 CNBs. Final excisional biopsy was benign in 24 of 27 cases (88%) with associated ductal carcinoma in-situ (DCIS) in 3 of 27 cases (11%). Eighteen of 27 (67%) CNBs were classified as focal while 9 (33%) were described as prominent. Zero of the 18 focal patients had a malignancy compared to 3 of the 9 in the prominent group (0% vs 33%, p=0.02). Of the 27 pure FEA CNBs, 6 patients had a personal history of breast carcinoma, five DCIS and one invasive ductal carcinoma. No malignancies were found in the 21 patients without a personal history of breast carcinoma versus three in the patients with a positive history (0/21 v 3/6, p=0.007). CONCLUSIONS: Our data suggests those women who have adequate sampling and sectioning of CNBs, with focal, pure FEA on pathology, and are without a personal history of breast cancer may undergo a period of imaging surveillance. Conversely, patients with a history of breast cancer or pure, prominent FEA on CNB disease should proceed to excisional biopsy.

Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion.

INTRODUCTION: Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. METHODS: Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. RESULTS: Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. CONCLUSIONS: Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.

A subset of morphologically distinct mammary myoepithelial cells lacks corresponding immunophenotypic markers.

INTRODUCTION: Immunostaining for smooth muscle actin (SMA) is commonly used to elucidate mammary myoepithelial (ME) cells, whose presence or absence is a reliable criterion for differentiating in situ and invasive carcinomas. However, some morphologically distinct ME cells fail to stain for SMA. This study intended to assess whether these SMA-negative cells also lack the expression of other ME cell markers. METHODS: Hematoxylin/eosin and SMA immunostained sections from 175 breast cancer patients were examined. Three cases were found to harbor ducts that showed morphologically distinct ME cell layers, but showed no SMA immunostaining in at least one-third of the layer or the entire layer. Eight additional consecutive sections from each case were stained for SMA, using a black chromogen, and each was then re-stained for one of eight additional markers supposed to exclusively or preferentially stain ME cells, using a red chromogen. SMA-negative ME cells were re-examined for the expression of other markers. RESULTS: SMA-negative ME cells in two cases also failed to display immunoreactivity for other markers, including calponin, CD10, smooth muscle myosin heavy chain, protease inhibitor 5 (maspin), Wilms' tumor-1, and cytokeratins 5, 14, and 17 (CK5, CK14, and CK17). However, in one case SMA-negative ME cells displayed immunoreactivities for maspin, CK5, CK14, and CK17. The distribution of these ME cells is independent of ductal size, length, and architecture. CONCLUSIONS: A subset of morphologically identifiable ME cells lack the expression of nine corresponding immunophenotypic markers, suggesting that ME cells might also be subject to different normal and pathological alterations.