Outcome of radial scar/complex sclerosing lesion associated with epithelial proliferations with atypia diagnosed on breast core biopsy: results from a multicentric UK-based study.

AIMS: The clinical significance of radial scar (RS)/complex sclerosing lesion (CSL) with high-risk lesions (epithelial atypia) diagnosed on needle core biopsy is not well defined. We aimed at assessing the upgrade rate to ductal carcinoma in situ (DCIS) and invasive carcinoma on the surgical excision specimen in a large cohort with RS/CSL associated with atypia. METHODS: 157 women with a needle core biopsy diagnosis of a RS/CSL with atypia and follow-up histology were studied. Histological findings, including different forms of the atypical lesions and final histological outcome in the excision specimens, were retrieved and analysed, and the upgrade rates for malignancy and for invasive carcinoma were calculated. RESULTS: 69.43% of the cases were associated with atypical ductal hyperplasia (ADH) or atypia not otherwise classifiable, whereas lobular neoplasia was seen in 21.66%. On final histology, 39 cases were malignant (overall upgrade rate of 24.84%); 12 were invasive and 27 had DCIS. The upgrade differed according to the type of atypia and was highest for ADH (35%). When associated with lobular neoplasia, the upgrade rate was 11.76%. The upgrade rate's variability was also considerably lower when considering the upgrade to invasive carcinoma alone for any associated lesion. CONCLUSIONS: The upgrade rate for ADH diagnosed on needle core biopsy with RS is similar to that of ADH without RS and therefore should be managed similarly. RS associated with lobular neoplasia is less frequently associated with malignant outcome. Most lesions exhibiting some degree of atypia showed a similar upgrade rate to invasive carcinoma. Management of RS should be based on the concurrent atypical lesion.

Impact of breast cancer grade discordance on prediction of outcome.

AIMS: Histological grade is an independent prognostic variable in breast cancer (BC). Previous concordance studies of BC grade have reported moderate levels of agreement; a typical finding in morphological assessment of biological variables. This study aimed to investigate the impact of discordance on the prognostic value of grade and to identify the best reporting approach in borderline cases. METHODS AND RESULTS: A large (n = 1675) well-characterised annotated cohort of BC, originally graded in routine practice using glass slides, was re-graded twice by an expert breast pathologist using virtual microscopy with a 3-month washout period. Outcome was assessed using breast cancer-specific and distant metastasis-free survival (median follow-up = 135 months). Fifty-eight per cent of the cases showed absolute agreement in the three separate grading sessions, whereas grades 1/2 and 2/3 discordance were observed in 21% and 21%, respectively. Absolute intra-observer agreement using virtual microscopy was observed in 77% of the cases, whereas 13% and 10% showed grades 1/2 and 2/3 discordance, respectively. Despite the concordance, outcome analysis revealed significant associations between tumour grade and patients' outcome in the three grading sessions. Grades 1/2 and 2/3 discordant cases showed intermediate survival between grades 1 and 2 tumours and grades 2 and 3 tumours, respectively. Grades 1/2 discordant cases showed a worse outcome when compared with grade 1 tumours (P = 0.008) but no statistical difference was identified when compared with grade 2 tumours. Similarly, grades 2/3 discordant cases showed a significant difference from grade 2 tumours (P < 0.001), but no statistical difference was identified when compared with grade 3 tumours. CONCLUSIONS: Breast cancer grade discordance is probably a reflection of biologically, and hence morphologically, borderline tumours. Cases with borderline features for grade are more likely to behave similarly to the higher-grade category. Repeating histological grade of borderline cases or double reporting may improve correlation with outcome.

Diagnostic concordance of reporting lymphovascular invasion in breast cancer.

AIMS: This study aims to assess the diagnostic agreement of lymphovascular invasion (LVI) in invasive breast cancer (BC). METHODS: Data on LVI were collected from the UK National Health Service Breast Screening Programme pathology external quality assurance scheme database. 101 BCs assessed over a 10-year period (2004-2014) were included. Cases were scored by an average of 600 pathologists. Three H&E stained slides from each case were reviewed by three pathologists and additional variables were evaluated. RESULTS: In the whole series, the overall κ value was 0.4 (range 0.26-0.53). On review, LVI was detected in all three slides in 20 cases (20%), in two slides in 12 cases and in one of the three slides in 9 cases and was not seen in 60 cases. For concordance analysis, the first and last groups were used to represent cases with definite (LVI+) and absent LVI (LVI-), respectively. In the LVI+group (n=20), the level of agreement ranged from 0.54 to 0.99 (median 0.86). In the LVI- group (n=60), the level of agreement ranged from 0.52 to 1.00 (median 0.93), with 44% of cases showing interobserver concordance of >95%. There was a correlation between increasing number of involved lymphovascular spaces in the section and higher LVI reporting concordance. Some degree of retraction/fixation artefacts was observed in 35% of cases; this was associated with a lower concordance rate. CONCLUSIONS: The concordance of reporting LVI is variable. Cases without LVI and those with multiple involved vessels are likely to have the highest concordance and the highest detection rates.