  Significance: Histopathological analysis of tissues is an essential tool for
grading, staging, diagnosing and resecting cancers and other malignancies.
Current histopathological techniques require substantial sample processing
prior to staining with hematoxylin and eosin (H&E) dyes, to highlight nuclear
and cellular morphology. Sample preparation and staining is resource-intensive
and introduces potential for variability during sample preparation.
  Aim: We present a novel method for direct label-free histopathological
assessment of formalin fixed paraffin embedded tissue blocks and thin tissue
sections using a dual contrast photoacoustic remote sensing (PARS) microscopy
system.
  Approach: To emulate the nuclear and cellular contrast of H&E staining, we
leverage unique properties of the PARS system. Here the ultraviolet excitation
of the PAARS microscope takes advantage of DNA's unique optical absorption to
provide nuclear contrast analogous to hematoxylin staining of cell nucelli.
Concurrently, the optical scattering contrast of the PARS detection system is
leveraged to provide bulk tissue contrast analogous to eosin staining of cell
membranes.
  Results: We demonstrate the efficacy of this technique by imaging human
breast tissue and human skin tissues in formalin fixed paraffin embedded tissue
blocks and frozen sections respectively. Salient nuclear and extra-nuclear
features such as cancerous cells, glands and ducts, adipocytes, and stromal
structures such as collagen.
  Conclusions. The presented dual contrast PARS microscope enables label-free
visualizations of tissue with contrast and quality analogous to the current
gold standard for histopathological analysis. Thus, the proposed system is well
positioned to augment existing histopathological workflows, providing
histological imaging directly on unstained tissue blocks and sections.
