Recognizing breast ductal carcinoma in situ on fine‐needle aspiration: A diagnostic dilemma

H, Guo; Zhang, Zhihui; Zhao, Huan; Zhao, Lidan; Pan, Qin-Jing

doi:10.1002/dc.23015

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Bonzanini et al [24],in their study of DCIS versus IDC, reported that tubular clusters were associated with IDC grade 1-2 in 89% of the cases. Guo et al [25 ]remarked on the exclusive association of tubular structures with invasive carcinoma, but that this finding was uncommon (11.5%). Our findings concur with these 2 studies.…”

Section: Discussionmentioning

confidence: 99%

The Microscopic Complexities of C3 in Breast Cytology

Weigner

Zardawi²,

Braye³

et al. 2014

Acta Cytologica

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Background: Fine-needle aspiration (FNA) of difficult breast lesions often results in an atypical (C3) report. The assortment of outcomes generated by C3 reports varies widely, and this has given rise to different clinical management pathways. Objective: To identify and objectively assess microscopic features associated with atypical/C3 breast FNA cases. Materials and Methods: A total of 230 atypical breast FNAs were subjected to a blind microscopic rescreen using a range of robust qualitative and quantitative cytological criteria including cellularity, architectural qualities, cytomorphology and background features. A logistic regression with a receiver operating characteristic (ROC) curve and the resultant forward stepwise analysis were conducted to assess the results. This statistical testing was measured against malignant, benign proliferative and benign non-proliferative outcomes. Results: The malignant and benign proliferative outcomes showed a mixture of opposing protective and predictive individual cytological criteria. The stepwise analysis produced models demonstrating the best combination of individual cytological criteria for malignancy, proliferative and benign non-proliferative entities. In the malignancy model, discohesion, nuclear crowding within sheets, diminished numbers of bare bipolar nuclei and myoepithelial cells, the presence of tubules or necrosis and the absence of a cystic background were important features. The benign proliferative model suggested the same criteria but with the opposite implication and with the addition of several others, such as the presence of apocrine metaplasia, retained polarity and a speckled or coarse chromatin pattern. Age was a significant factor in malignant and proliferative outcomes. The benign non-proliferative stepwise analysis produced a model with fewer criteria (complex sheets, bare bipolar nuclei and a cystic background) limiting clinical application. Conclusion: Atypical/C3 breast cytology remains a legitimate reporting category. However, it is associated with a number of different histological outcomes. The incidence of the C3 category can be significantly reduced by controlling extrinsic factors and understanding the associated microscopic features.

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Section: Discussionmentioning

confidence: 99%

The Microscopic Complexities of C3 in Breast Cytology

Weigner

Zardawi²,

Braye³

et al. 2014

Acta Cytologica

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“…The protein wash seen in cystic change can be confused with serum or the wet background associated with DCIS. Necrosis can produce a fluid like sample but ghost cells and nuclear debris should heighten suspicion and not be confused with a cystic background . Difficulties can arise when extracellular mucin associated with mucinous breast lesions is mistaken for a cystic background.…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of diagnostic criteria associated with atypical breast cytology

Weigner

Zardawi²,

Braye

et al. 2017

Cytopathology

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Interobserver and intraobserver variability remains a significant challenge for cytologists. Despite attempts to define significant criteria associated with C3, good reproducibility could not be achieved. The C3 category is imprecise and highlights the inadequacy of the current classification reporting categories for breast FNA. The impending review of reporting breast cytology by the International Academy of Cytology is timely and appropriate.

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“… 4 , 5 , 39 These stromal changes and hyperproliferative epithelium are similar to the changes observed with ductal carincoma in situ of the breast, leading to the speculation that defective apoptotic cell clearance may provide a catalyst for breast cancer development. 53 , 54 , 55 , 56 , 57 In addition, the immunosuppressive immune milieu associated with clearance of apoptotic cells by the mammary epithelium has also been proposed to contribute to breast cancer progression. 58 , 59 Women have a transient increase in breast cancer risk during the postpartum period and breast cancers diagnosed postpartum have poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Mammary epithelial cell phagocytosis downstream of TGF-β3 is characterized by adherens junction reorganization

et al. 2015

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After weaning, during mammary gland involution, milk-producing mammary epithelial cells undergo apoptosis. Effective clearance of these dying cells is essential, as persistent apoptotic cells have a negative impact on gland homeostasis, future lactation and cancer susceptibility. In mice, apoptotic cells are cleared by the neighboring epithelium, yet little is known about how mammary epithelial cells become phagocytic or whether this function is conserved between species. Here we use a rat model of weaning-induced involution and involuting breast tissue from women, to demonstrate apoptotic cells within luminal epithelial cells and epithelial expression of the scavenger mannose receptor, suggesting conservation of phagocytosis by epithelial cells. In the rat, epithelial transforming growth factor-β (TGF-β) signaling is increased during involution, a pathway known to promote phagocytic capability. To test whether TGF-β enhances the phagocytic ability of mammary epithelial cells, non-transformed murine mammary epithelial EpH4 cells were cultured to achieve tight junction impermeability, such as occurs during lactation. TGF-β3 treatment promoted loss of tight junction impermeability, reorganization and cleavage of the adherens junction protein E-cadherin (E-cad), and phagocytosis. Phagocytosis correlated with junction disruption, suggesting junction reorganization is necessary for phagocytosis by epithelial cells. Supporting this hypothesis, epithelial cell E-cad reorganization and cleavage were observed in rat and human involuting mammary glands. Further, in the rat, E-cad cleavage correlated with increased γ-secretase activity and β-catenin nuclear localization. In vitro, pharmacologic inhibitors of γ-secretase or β-catenin reduced the effect of TGF-β3 on phagocytosis to near baseline levels. However, β-catenin signaling through LiCl treatment did not enhance phagocytic capacity, suggesting a model in which both reorganization of cell junctions and β-catenin signaling contribute to phagocytosis downstream of TGF-β3. Our data provide insight into how mammary epithelial cells contribute to apoptotic cell clearance, and in light of the negative consequences of impaired apoptotic cell clearance during involution, may shed light on involution-associated breast pathologies.

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Recognizing breast ductal carcinoma in situ on fine‐needle aspiration: A diagnostic dilemma

Cited by 4 publications

References 11 publications

The Microscopic Complexities of C3 in Breast Cytology

The Microscopic Complexities of C3 in Breast Cytology

Reproducibility of diagnostic criteria associated with atypical breast cytology

Mammary epithelial cell phagocytosis downstream of TGF-β3 is characterized by adherens junction reorganization

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