Question

How deep learning is poised to revitalize histomorphology for personalized cancer care?

Answer 1

Accurate interpretation of the hematoxylin and eosin (H&E) slide has remained the foundation of pathological analysis and diagnostic medicine for over a century.1 For the pathologist, the H&E slide is equivalent to a high-quality patient history or physical exam. It combines art and science to help triage and guide more focused and specialized ancillary studies. Unfortunately, the perceived value of histomorphologic analysis in the era of precision medicine is diminishing in recent years due to the emergence of more contemporary and data-rich molecular studies.2,3,4 Ironically, this is no different than the scrutiny that the patient history and physical exam have faced, in light of widely available whole-body imaging technologies.5,6,7 Some have even proposed that given the exponential decrease in sequencing costs, medical assessment could effectively begin with whole-genome analysis.8 Here, we discuss the current state and the possible future of the H&E stain by highlighting some of its strengths and shortcomings. It may well be that the scrutiny that the H&E microscopic exam has faced in recent years4 is no fault of its own, but the lack of effective approaches to routinely extract more of the rich morphologic information it contains.

The H&E slide continues to be a valuable tool for pathologists and clinicians alike. For example, quite often, surgeons request urgent intra-operative pathological interpretations to help guide surgery. This clinical scenario often necessitates that an accurate diagnosis be rendered within 5–10 min. The outcome usually has huge implications for the trajectory of the remaining surgery (e.g., extent of resection, triaging additional laboratory tests). As a result, most surgeons have a strong preference for the expert opinion of highly subspecialized pathologists (e.g., from a neuropathologist for neurosurgical intra-operative consults). Until molecular or alternative analytic approaches become compatible with these acute timeframes, the H&E slide will continue to be an essential tool to help guide surgical care.

The H&E slide also has a key role in precision oncology in sub-acute settings. Technological advances now allow patients’ tumors to be globally profiled at the genomic, epigenomic, transcriptomic, proteomic, phosphoproteomic, and other -omic levels.3, 9, 10 This list of molecular tests, each with their own strengths and weaknesses, continues to grow. However, even with decreasing costs of sequencing, performing routine multi-platform molecular analysis on every specimen will likely not become a time-effective or cost-effective strategy in the foreseeable future. This relatively high cost of multi-omic analysis will continue to necessitate molecular triaging to help narrow testing to those most appropriate for the specific tumor type and clinical scenario. Lastly, the H&E slide still remains one of the most versatile diagnostic tools when only minute amounts of tissue, insufficient for molecular analysis, is available. Similarly, unlike bulk tissue-based molecular tests, microscopic analysis preserves important region-to-region, single-cell-level spatial information that may have significant implications for diagnostic and treatment decisions.11, 12 For example, even for tumors that have been analyzed at the molecular level, treatment regimens can dramatically change when specific microscopic features are noted (e.g., lymphovascular invasion, metastatic foci, elevated mitotic activity,13 tumor morphology).14 Therefore, there are many compelling reasons to retain the H&E exam as a non-overlapping and essential tool in our growing precision oncology toolbox.

Perhaps a major limitation of the H&E slide in the era of “big-data” is the unassisted human interpretation currently used for analysis. To promote consistency and objective inter-observer agreement, most pathologists are trained to follow simple algorithmic decision trees that sufficiently stratify patients into reproducible groups b

Answer 2

Answer:

Perhaps a major limitation of the H&E slide in the era of “big-data” is the unassisted human interpretation currently used for analysis. To promote consistency and objective inter-observer agreement, most pathologists are trained to follow simple algorithmic decision trees that sufficiently stratify patients into reproducible groups b