Figure 6. Neuroendocrine differentiation is observed in diffuse cancers of the NE-high and NE-low molecular types but not in the EBV-positive type.

(A) Solid carcinoma of EBV-positive molecular type is negative for chromogranin (B) and synaptophysin (C) with positive internal control in the neuroendocrine cells of residual non-neoplastic gastric pits (insets in B and C). (D) A carcinoma of NE-high molecular type and infiltrating isolated-cell histology has scattered individual malignant cells expressing chromogranin (E) and synaptophysin (arrows, F). (G) Similarly, a signet ring cell carcinoma of NE-high molecular type has chromogranin (H) and synaptophysin expressing cells (arrows, I). Synaptophysin also highlights small nerve twigs within the abundant fibrous stroma (arrowheads, F and I). (J-O) An infiltrative carcinoma of NE-low molecular type has focal areas of small nests and short cords of cells with enlarged vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm (J), other focal areas in which the nests of eosinophilic cells have admixed signet ring cells (K), but predominantly the tumor consists of eosinophilic and signet ring cells infiltrating singly (M). All three of these tumor morphologies are embedded in dense fibrous stroma. Nested areas have individual chromogranin positive cells within the nests (L). The singly infiltrating eosinophilic cells are chromogranin positive and synaptophysin negative while the signet ring cells have the reverse pattern—chromogranin negative and synaptophysin positive (N,O).