Large Granular Lymphocyte Leukemia or Fischer Rat Leukemia

Etiology:  A spontaneous leukemia with circulating atypical mononuclear cells containing azurophilic cytoplasmic granules has been reported in aged Fischer 344 (F344) rats.

Incidence:  The mononuclear cell leukemia is one of the most common neoplasms in aged F344 rats and is frequently referred to as Fischer Rat Leukemia.

Clinical Signs:  Clinically, leukocytosis with up to 90% atypical mononuclear cells and anemia are observed.

Pathology:  Splenomegaly, hepatomegaly and lymphadenopathy are seen at necropsy. Tissue enlargement is due to massive infiltration of the sinusoids with large, undifferentiated lymphocytes with oval nuclei.  The kidneys are often grey due to the deposition of brown, iron positive granules in the proximal tubules.  Leukemic cells appear to be of natural killer (NK) cell origin.

Diagnosis: Diagnosis can be made by performing a blood smear or upon necropsy with histopathology of the spleen.