Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma Staging.

Histomorphologic prognostic biomarkers that can be measured using only an hematoxylin and eosin stain are very attractive because they are simple and cheap. We conceived an entirely novel biomarker of this type, the Breslow density (BD), which measures invasive melanoma cell density at the site where Breslow thickness (BT) is measured. This study assessed BD's prognostic value. In this study, BD was measured in 1329 melanoma patients. Measurement accuracy and precision was assessed using intraclass correlation coefficient (ICC). Survival was assessed with a primary end-point of melanoma-specific survival (MSS) and also overall survival and metastasis-free survival. We found that BD measurement was accurate compared with gold standard image analysis (ICC, 0.84). Precision was excellent for 3 observers with different experience (ICC, 0.93) and for an observer using only written instructions (ICC, 0.93). BD was a highly significant predictor in multivariable analysis for overall survival, MSS, and metastasis-free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD together had best explanatory capability. A BD cut point of ≥65% was trained in 970 melanomas and validated in 359. This cut point showed promise as a novel way to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a targeted burden score. This was a validated as an adjunct to American Joint Committee on Cancer stage. In summary, BD can be measured accurately and precisely. It demonstrated independent prognostic value and explained MSS better than BT alone. Notably, we demonstrated ways that BD could be used with American Joint Committee on Cancer version 8 staging.

High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity.

AIMS: Encapsulated papillary carcinoma (EPC) is a recognized special type of breast carcinoma. Despite compelling evidence indicating its invasive nature, although not of a conventional form, the current consensus is to manage EPC as an in-situ disease, based on its indolent clinical behaviour. Although most EPCs are recognized to be of low and intermediate grade, a distinct proportion of these tumours do show high cytonuclear grade features. The existence and behaviour of these rare high-grade variants remains to be defined. We aim to characterise these tumours and provide evidence to guide their management. METHODS AND RESULTS: In this study, we have identified 12 high-grade EPCs without associated conventional stromal invasion. To further characterize these high-grade tumours, a series of invasive papillary carcinomas (n = 30) were assessed for the coexistence of EPC. The literature was also reviewed. Approximately 3% of pure EPCs showed high-grade features as defined by nuclear pleomorphism and increased mitotic activity. These tumours not only showed histological features associated with aggressive behaviour, but were also often hormone receptor-negative, tended to be of larger size, and were more frequently associated with stromal invasion. Of the 10 patients with follow-up data, one with pure high-grade EPC developed recurrence and died of her disease. CONCLUSION: High-grade EPC is rare, and its histological features and more aggressive clinical behaviour suggest that consideration should be given to managing it in a similar fashion to conventional forms of invasive breast carcinoma, based on established clinicopathological parameters.