Comparative ultrastructural study of cytotoxic granules in nasal natural killer cell lymphoma, intestinal T-cell lymphoma, and anaplastic large cell lymphoma

Comparative immunohistochemical and ultrastructural studies were performed on five nasal natural killer (NK) cell lymphoma cases, two intestinal T-cel l lymphoma cases, and eight anaplastic large cell lymphoma (ALCL) cases to clarify morphological differences in cytotoxic granules among these cytotox ic lymphomas. Nasal NK-cell lymphomas and intestinal T-cell lymphomas had f ine azurophilic granules and displayed dot-like immunostaining of granzyme B- and T-cell intracellular antigen 1 (TIA-1), predominantly in the central area of the cytoplasm. Ultrastructurally, these NK-cell lymphomas and inte stinal T-cell lymphomas had two types of cytotoxic granules, type-I granule s (dense core granules) and type-II granules (multivesicular bodies), which have been demonstrated in normal large granular lymphocytes in peripheral blood. However, ALCLs did not have azurophilic granules, and only type-II c ytotoxic granules were found ultrastructurally, even though they showed sim ilar dot-like immunostained patterns of granzyme B and TIA-1, as seen in NK -cell lymphomas and intestinal T-cell lymphomas. Immunoelectron microscopy revealed that TIA-1 was primarily located at the periphery of the cytoplasm ic granules in the NK-cell lymphoma and ALCL cases. These findings suggest that malignant lymphomas with a cytotoxic phenotype can be divided into two types, (azurophilic granule)(+), (type-I granule)(+), (type-II granule)(+) lymphomas and (azurophilic granule)(-), (type-I granule)(-), (type-II gran ule)(+) lymphomas.