Quantifying Hidden Architectural Patterns in Metaplastic Tumors by Calculating the Quadrant-Slope Index (QSI)

The Quadrant-Slope Index (QSI) method was created in order to detect subtle patterns of organization in tumor images that have metaplastic elements, such as streams of spindle cells [1]. However, metaplastic tumors also have nuclei that may be aligned like a stream but are not obvious to the pathologist because the shape of the cytoplasm is unclear. The previous method that I developed, the Nearest-Neighbor Angular Profile (N-NAP) method [2], is good for detecting subtle patterns of order based on the assumption that breast tumor cells are attempting to arrange themselves side-by-side (like bricks), as in the luminal compartment of a normal mammary gland [3]. However, this assumption is not optimal for detecting cellular arrangements that are head-to-tail, such as in streams of spindle cells. Metaplastic carcinomas of the breast (i.e. basal-like breast cancers, triple-negative breast cancers) are believed to be derived from the stem or progenitor cells that reside in the basal/myoepithelial compartment of the normal mammary gland [Reviewed in 3]. Epithelial cells in the basal/myoepithelial compartment arrange themselves in an head-to-tail fashion, forming a net that surrounds the luminal compartment [3,4]. If cancer cells in a metaplastic tumor are trying to be normal, the optimal way to detect subtle regions of them attempting to be ordered normally should highlight the head-to-tail alignment of cells.