Immunostaining of an ALK-positive lymphoma bearing the t(2;5) translocation (top left and right). (Top left) Immunostaining for ALK protein. Tumor cells (arrow) show strong cytoplasmic and nuclear ALK expression. Residual lymphoid tissue is ALK-negative (original magnification × 800). (Top right) Tumor cells (arrow) show cytoplasmic and nuclear positivity for the N-terminus of NPM (N-NPM). Cytoplasmic positivity reflects immunostaining of the NPM moiety of the NPM-ALK fusion protein. Normal residual lymphoid cells (arrowhead) show wild-type nucleus-restricted NPM staining (original magnification × 800). In contrast, immunostaining for the C-terminus of NPM showed a nucleus-restricted expression of the protein (not shown). (Bottom left and right) An example of ALK-positive lymphoma expressing variant ALK fusion protein. (Bottom left) Positivity for the ALK protein is restricted to the cytoplasm of the large anaplastic tumor cells (arrowhead; original magnification × 1,000; right). The N-terminus of NPM (N-NPM) shows nucleus-restricted expression both in tumor cells (arrowhead) and in a normal endothelial cell (arrow), reflecting immunostaining of wild-type NPM (original magnification × 1,000). An identical staining pattern (not shown) was observed for the C-terminus of NPM. (APAAP immunostaining on lymph node paraffin sections; hematoxylin counterstaining.)