Fig. 2: Histopathological Rreview outlining key features noted post-treatment with immunotherapy.

Histopathologic review was based on surgical specimens of the tumors post-treatment that were entirely submitted for the two patients showing marked therapeutic response. Microscopically, a dense mixed inflammatory infiltrate was identified surrounding the tumor mass in Patient 2 (A). The infiltrate was lymphoplasmacytic-rich but also contained frequent macrophages (some foamy), occasional multinucleated giant cells, eosinophils, and neutrophils (B). Tertiary lymphoid structures (TLS) or Crohn like reaction was commonly seen at the periphery (C). Neovascularization was a prominent feature in most tumor beds, and granulation tissue predominated along the luminal surface (D). A similar response was noted in Patient 1. Rather than haphazardly arranged within dense fibrosis, as is often seen with neoadjuvant chemotherapy, viable tumor was often superficially oriented near the luminal surface within the tumor center, with dense inflammation surrounding the periphery and comprising most of the grossly identifiable tumor bed (E). Residual tumor glands often demonstrated evidence of ongoing destruction with incomplete lumens and frequent luminal microabscesses (F).