Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?

Abstract

Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-alpha. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

“…None of our tested usual ductal hyperplasia and blunt duct adenosis lesions showed whole-arm losses of 16q. This confirms that, although some ADH, atypical ductal hyperplasia; BDA, blunt duct adenosis; CCL−, columnar cell lesion without atypia; DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; UDH, usual ductal hyperplasia authors considered blunt duct adenosis to be a synonym of columnar cell lesion (without atypia) [45][46][47] or a growth pattern of columnar cell lesions [48], this lesion seems to be a separate entity and no precursor lesions of low-grade breast neoplasia. And this underlines the importance of morphologically discriminating blunt duct adenosis from columnar cell lesion.…”

Columnar Cell Lesion and Apocrine Hyperplasia of the Breast: Is There a Common Origin? The Role of Prolactin-induced Protein

“…However, the risk assessment of each nonmalignant lesion has by no means fully clarified. 4,5,9,14,36,37 In particular, apocrine metaplasia and AH represent 2 distinct types of alterations within the fibrocystic changes spectrum and almost invariably display strong and diffuse PIP expression. 14,25 The role of this polypeptide, however, has never been explored in associated CCLs.…”

Evidence for a Dualistic Model of High-grade Serous Carcinoma

“…17,18 Another tumor phenotype, luminal A, is associated with defined precursors, develops more slowly, and as expected is more likely to be detected on screening studies. [19][20][21] Additional studies are introducing dualistic classifications of HGSC in BRCA + and BRCA À women that correlate molecular profiles with outcome. 22,23 In parallel with arguments for multiple tumor origins, others have divided tumors prognostically into ovarian surface or tubal origin on the basis of expression signatures.…”