Observer agreement comparing the use of virtual slides with glass slides in the pathology review component of the POSH breast cancer cohort study

Shaw, Emily; Hanby, Andrew M.; Wheeler, Kevin; Shaaban, Abeer M.; Poller, David; Barton, Sheila J.; Treanor, Darren; Fulford, Laura; Walker, Rosemary A.; Ryan, D; Lakhani, Sunil R.; Wells, Clive; Roché, H.; Theaker, J.M.; Ellis, Ian O.; Jones, J. Louise; Eccles, Diana

doi:10.1136/jclinpath-2011-200369

Cited by 29 publications

(23 citation statements)

References 12 publications

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“…Exact grade agreement between WSI and LM grading was reached in 68% of cases. This magnitude of concordance is in line with a prior reproducibility study 23. Since WSI has a procedural difference, compared with LM, some emphasis was given to Cramer’s V as measure of concordance.…”

Section: Discussionsupporting

confidence: 81%

Breast cancer histologic grading using digital microscopy: concordance and outcome association

et al. 2018

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AimsVirtual microscopy utilising digital whole slide imaging (WSI) is increasingly used in breast pathology. Histologic grade is one of the strongest prognostic factors in breast cancer (BC). This study aims at investigating the agreement between BC grading using traditional light microscopy (LM) and digital WSI with consideration of reproducibility and impact on outcome prediction.MethodsA large (n=1675) well-characterised cohort of BC originally graded by LM was re-graded using WSI. Two separate virtual-based grading sessions (V1 and V2) were performed with a 3-month washout period. Outcome was assessed using BC-specific and distant metastasis-free survival.ResultsThe concordance between LM grading and WSI was strong (LM/WSI Cramer’s V: V1=0.576, and V2=0.579). The agreement regarding grade components was as follows: tubule formation=0.538, pleomorphism=0.422 and mitosis=0.514. Greatest discordance was observed between adjacent grades, whereas high/low grade discordance was uncommon (1.5%). The intraobserver agreement for the two WSI sessions was substantial for grade (V1/V2 Cramer’s V=0.676; kappa=0.648) and grade components (Cramer’s V T=0.628, p=0.573 and M=0.580). Grading using both platforms showed strong association with outcome (all p values <0.001). Although mitotic scores assessed using both platforms were strongly associated with outcome, WSI tends to underestimate mitotic counts.ConclusionsVirtual microscopy is a reliable and reproducible method for assessing BC histologic grade. Regardless of the observer or assessment platform, histologic grade is a significant predictor of outcome. Continuing advances in imaging technology could potentially provide improved performance of WSI BC grading and in particular mitotic count assessment.

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Section: Discussionsupporting

confidence: 81%

Breast cancer histologic grading using digital microscopy: concordance and outcome association

et al. 2018

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“…Fourteen cases had insufficient tumour for the study and were excluded. Of the remaining 45 cases, Morphological assessment was included for 60 young onset cases with a germline BRCA1 pathogenic variant (group 3), 61 young onset cases with a germline BRCA2 pathogenic variant (group 4) and 98 young onset breast cancer cases (group 5) with no identifiable germline high risk pathogenic variant (BRCA1, BRCA2 or TP53) [21].…”

Section: Resultsmentioning

confidence: 99%

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study)

Packwood

Martland

Sommerlad

et al. 2019

The Journal of Pathology CR

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Germline TP53 pathogenic variants are rare but associated with a high risk of cancer; they are often identified in the context of clinically diagnosed Li–Fraumeni syndrome predisposing to a range of young onset cancers including sarcomas and breast cancer. The study aim was to conduct a detailed morphological review and immuno‐phenotyping of breast cancer arising in carriers of a germline TP53 pathogenic variant. We compared breast cancers from five defined groups: (1) TP53 carriers with breast cancer ( n = 59), (2) early onset HER2‐amplified breast cancer, no germline pathogenic variant in BRCA1/2 or TP53 ( n = 55), (3) BRCA1 pathogenic variant carriers ( n = 60); (4) BRCA2 pathogenic variant carriers ( n = 61) and (5) young onset breast cancer with no known germline pathogenic variant ( n = 98). Pathologists assessed a pre‐agreed set of morphological characteristics using light microscopy. Immunohistochemistry (IHC) for HER2, ER, PR, p53, integrin alpha v beta 6 (αvβ6) integrin, α‐smooth muscle actin (α‐SMA) and pSMAD2/3 was performed on tissue microarrays of invasive carcinoma. We confirmed a previously reported high prevalence of HER2‐amplified, ductal no special type invasive breast carcinoma amongst known TP53 germline pathogenic variant carriers 20 of 36 (56%). Furthermore we observed a high frequency of densely sclerotic tumour stroma in cancers from TP53 carriers (29/36, 80.6%) when compared with non‐carriers, 50.9% (28/55), 34.7% (50/144), 41.4% (65/157), 43.8% (95/217) in groups 2–5 respectively. The majority of germline TP53 gene carrier breast tumours had a high intensity of integrin αvβ6, α‐SMA and pSMAD2/3 expression in the majority of cancer cells. In conclusion, aggressive HER2 positive breast cancers with densely sclerotic stroma are common in germline TP53 carriers. High levels of αvβ6 integrin, α‐SMA and pSMAD2/3 expression suggest that the dense stromal phenotype may be driven by upregulated transforming growth factor beta signalling.

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“…An important initial step in the wider adoption of this technology is the establishment of validation data assessing how effective pathologists are using digital workstations in comparison with conventional light microscopes and glass slide microscopy (GS) when examining cases for primary diagnosis. Previous studies using a range of differing technologies in different clinical settings have reported the comparison of DP with GS, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] and criteria for such comparisons have been published. 18 However, although most of these studies have shown promise, no single study has been sufficiently powered to demonstrate a statistically significant equivalence (i.e.…”

Section: Introductionmentioning

confidence: 99%

Validation of digital pathology imaging for primary histopathological diagnosis

et al. 2015

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Aims: Digital pathology (DP) offers advantages over glass slide microscopy (GS), but data demonstrating a statistically valid equivalent (i.e. non-inferior) performance of DP against GS are required to permit its use in diagnosis. The aim of this study is to provide evidence of non-inferiority. Methods and results: Seventeen pathologists rereported 3017 cases by DP. Of these, 1009 were re-reported by the same pathologist, and 2008 by a different pathologist. Re-examination of 10 138 scanned slides (2.22 terabytes) produced 72 variances between GS and DP reports, including 21 clinically significant variances. Ground truth lay with GS in 12 cases and with DP in nine cases. These results are within the 95% confidence interval for existing intraobserver and interobserver variability, proving that DP is non-inferior to GS. In three cases, the digital platform was deemed to be responsible for the variance, including a gastric biopsy, where Helicobacter pylori only became visible on slides scanned at the 960 setting, and a bronchial biopsy and penile biopsy, where dysplasia was reported on DP but was not present on GS. Conclusions: This is one of the largest studies proving that DP is equivalent to GS for the diagnosis of histopathology specimens. Error rates are similar in both platforms, although some problems e.g. detection of bacteria, are predictable.

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Observer agreement comparing the use of virtual slides with glass slides in the pathology review component of the POSH breast cancer cohort study

Abstract: Virtual slides represent an acceptable methodology for central review of breast cancer histopathology and can circumvent the need for either travel to view material, or the potential problems of sending it by post.

Cited by 29 publications

References 12 publications

Breast cancer histologic grading using digital microscopy: concordance and outcome association

Breast cancer histologic grading using digital microscopy: concordance and outcome association

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study)

Validation of digital pathology imaging for primary histopathological diagnosis

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