Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast

Elston, C. W.; Sloane, J P; Amendoeira, Isabel; Apostolikas, N.; Jp, Bellocq; Bianchi, Simonetta; Boecker, Werner; Bussolati, Gianni; Coleman, D; Connolly, C. E.; Dervan, P.; Drijkoningen, Maria; Eusebi, Vincenzo; Faverly, D.; Holland, R.; Jacquemier, Jocelyne; Lacerda, Manuela; Martínez-Peñuela, J.M.; Miguel, C. De; Moss, Susan; Munt, C; Peterse, Johannes L.; Rank, Fritz; Reiner, Angelika; Sylvan, M.; Wells, Clive; Zafrani, B

doi:10.1016/s0959-8049(00)00181-7

Cited by 84 publications

(57 citation statements)

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“…These results are similar to studies by Palli et al 8 and MacGrogan et al, 23 with the lowest category specific k-values for the diagnosis of atypical ductal hyperplasia (0.38 and 0.36, respectively). We agree with Elston et al, 21 who stated that the poor consistencies observed in the diagnosis of atypical ductal hyperplasia lesions raises serious concerns regarding the robustness of the current diagnostic criteria. Their use of digitized images serving the function of marked specific fields did not improve the k-values.…”

Section: Discussionsupporting

confidence: 90%

“…Most of the studies investigating concordance rates documented that high interobserver variation was mostly due to problems in differentiating atypical ductal hyperplasia and low-grade ductal carcinoma in situ. 8,11,[19][20][21][22] The category specific k-value was lowest for atypical ductal hyperplasia (0.43 for stages 1 and 2) in this study. These results are similar to studies by Palli et al 8 and MacGrogan et al, 23 with the lowest category specific k-values for the diagnosis of atypical ductal hyperplasia (0.38 and 0.36, respectively).…”

Section: Discussioncontrasting

confidence: 49%

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Atypical ductal hyperplasia: interobserver and intraobserver variability

et al. 2011

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Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter-and intraobserver variability and the impact of the addition of an immunostain for high-and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair (j-value ¼ 0.34). The intraobserver j-value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall j-value ¼ 0.50) was observed (P ¼ 0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter-and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 49%

Atypical ductal hyperplasia: interobserver and intraobserver variability

et al. 2011

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“…The subjectivity of interpreting breast lesions when quantitative criteria are used (atypical ductal hyperplasia versus ductal carcinoma in situ and papilloma versus papilloma with atypia or papillary carcinoma) has been well addressed in the pathology literature. [18][19][20] The cases that were discrepant in our study were the types of lesions that generally cause variability in interpretation. It is to be noted that variability in the histologic interpretations, which resulted from failure to recognize focal tissue changes or changes in the final categorization between reads, occurred in both WSI and OM.…”

Section: Commentmentioning

confidence: 65%

Multi-Institutional Comparison of Whole Slide Digital Imaging and Optical Microscopy for Interpretation of Hematoxylin-Eosin–Stained Breast Tissue Sections

Krishnamurthy¹,

Mathews²,

McClure³

et al. 2013

Archives of Pathology & Laboratory Medicine

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Context.-Whole slide imaging (WSI) is now used for educational purposes, for consultation, and for archiving and quantitation of immunostains. However, it is not routinely used for the primary diagnosis of hematoxylineosin-stained tissue sections.Objective.-To compare WSI using the Aperio digital pathology system (Aperio Technologies, Inc, Vista, California) with optical microscopy (OM) for the interpretation of hematoxylin-eosin-stained tissue sections of breast lesions.Design.-The study was conducted at 3 clinical sites; 3 breast pathologists interpreted 150 hematoxylin-eosinstained slides at each site, 3 times each by WSI and 3 times each by OM. For WSI, slides were scanned using an Aperio ScanScope and interpreted on a computer monitor using Aperio ImageScope software and Aperio Spectrum data management software. Pathologic interpretations were recorded using the College of American Pathologists breast checklist. WSI diagnoses were compared with OM diagnoses for accuracy, precision (interpathologist variation), and reproducibility (intrapathologist variation). Results were considered accurate only if the interpretation matched exactly between WSI and OM. The proportion of accurate results reported by each pathologist was expressed as a percentage for the comparison of the 2 platforms.Results.-The accuracy of WSI for classifying lesions as not carcinoma or as noninvasive (ductal or lobular) or invasive (ductal, lobular, or other) carcinoma was 90.5%. The accuracy of OM was 92.1%. The precision and reproducibility of WSI and OM were determined on the basis of pairwise comparisons (3 comparisons for each slide, resulting in 36 possible comparisons). The overall precision of WSI was 90.5% in comparison with 92.1% for OM; reproducibility of WSI was 91.6% in comparison with 94.5% for OM, respectively.Conclusions.-In this study, we demonstrated that WSI and OM have similar accuracy, precision, and reproducibility for interpreting hematoxylin-eosin-stained breast tissue sections. Further clinical studies using routine surgical pathology specimens would be useful to confirm these findings and facilitate the incorporation of WSI into diagnostic practice. (Arch Pathol Lab Med. 2013;137:1733-1739 doi: 10.5858/arpa.2012-0437-OA) T he practice of surgical pathology relies on image-based light microscopy diagnosis, which enables the detailed evaluation of the cytologic and architectural features of hematoxylin-eosin (H&E)-stained tissue sections. Significant recent technological advancements have allowed for the acquisition and storage of high-quality digital images. Several commercially available platforms are available for scanning H&E-stained tissue sections, generating digital whole slide images (WSI) for viewing and interpretation. The field of digital pathology is rapidly evolving toward the creation of a digital environment for interpreting and managing pathologic information contained in a glass slide.Several applications of digital pathology are currently being embraced by pathologists. Whole slide imaging is ...

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“…2 The difficulty in distinguishing between different papillary lesions recapitulates the problem in distinguishing between other intraductal epithelial proliferations that are non-papillary in nature. [5][6][7] In addition to routine hematoxylin and eosin-stained sections, various immunohistochemical markers have been used to aid in the distinction between such intraductal epithelial proliferations. Of these, high-molecular weight cytokeratins (CKs) traditionally expressed by the basal epithelial/myoepithelial cells of normal breast, including those detected by the 34bE12 antibody (CK1, CK5, CK10 and CK14) and CK6, have been useful in evaluating both nonpapillary [8][9][10][11] and papillary [12][13][14][15] lesions.…”

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confidence: 99%

Luminal cytokeratin expression profiles of breast papillomas and papillary carcinomas and the utility of a cytokeratin 5/p63/cytokeratin 8/18 antibody cocktail in their distinction

et al. 2011

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Luminal cytokeratin (CK) expression in breast papillary lesions, and its potential diagnostic utility among other markers in distinguishing between papillomas and papillary carcinomas, has not been previously evaluated. Such expression was determined in 42 papillary lesions (18 papillary carcinomas and 24 papillomas) by immunostaining with a CK5/p63/CK8/18 antibody cocktail. The mean CK8/18 intensity score and percentage of positive cells were significantly higher in papillary carcinomas (227 and 95%, respectively, vs 86 and 42% in papillomas; both P-values o0.0001), whereas the mean CK5 intensity score and percentage of positive cells were significantly lower (7 and 5%, respectively, vs 107 and 58% in papillomas; both P-values o0.0001). Half (9/18) of the papillary carcinomas expressed p63 vs all (24/24) of the papillomas (P ¼ 0.0001). P63 expression in papillary carcinoma was always (9/9; 100%) focal/limited in nature (expression in o10% of cells), whereas focal expression was seen in only four (17%) papillomas (Po0.0001). Both differential CK (CK8/18 and CK5) expression and p63 were equally sensitive (100%) for the diagnosis of papillary carcinoma, but differential CK expression was more specific (96 vs 83%), resulting in a greater accuracy. However, the best discriminatory power in the distinction from papilloma was achieved when all three markers were used in combination, resulting in 100% sensitivity and specificity values. It is concluded that breast papillary lesions have differential CK expression profiles that, especially in combination with p63, can be useful for their stratification, potentially also in needle biopsy material, in which more accurate and reproducible characterization is needed. Modern Pathology (2011) 24, 185-193; doi:10.1038/modpathol.2010; published online 12 November 2010 Keywords: breast; cytokeratin 5; cytokeratin 8/18; luminal cytokeratin; p63; papillary carcinoma; papilloma By comprising only 1-2% of breast lesions, 1 papillary lesions are relatively rare. Despite that, recognizing that a breast lesion is papillary in nature is not particularly difficult for pathologists. On the other hand, distinguishing between various types of papillary lesions can be problematic. 2,3 Such lesions include intraductal papilloma, intraductal papilloma with atypical ductal hyperplasia, intraductal papilloma with ductal carcinoma in-situ, papillary ductal carcinoma in-situ, intracystic

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Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast

Cited by 84 publications

References 13 publications

Atypical ductal hyperplasia: interobserver and intraobserver variability

Atypical ductal hyperplasia: interobserver and intraobserver variability

Multi-Institutional Comparison of Whole Slide Digital Imaging and Optical Microscopy for Interpretation of Hematoxylin-Eosin–Stained Breast Tissue Sections

Luminal cytokeratin expression profiles of breast papillomas and papillary carcinomas and the utility of a cytokeratin 5/p63/cytokeratin 8/18 antibody cocktail in their distinction

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