An IRONic case of PIMA

An 8-year-old spayed female Labrador retriever that was presented for a wellness examination at a referring practice had mild anemia with a hematocrit that progressed from 32% to 25% over the next 5 weeks. The dog's reticulocyte concentration was 26 400/μL on day 23, supporting nonregenerative anemia, and no cause was apparent from clinical and laboratory findings. This prompted the submission of bone marrow core and aspirate samples to our laboratory on day 38. These revealed ineffective erythroid hyperplasia with complete maturation but a predominance of rubricytes, rubriphagocytosis, mild lymphoplasmacytosis, and mild to regionally severe collagen myelofibrosis, all supportive of precursor-targeted immune-mediated anemia (PIMA).¹ Hemosiderin was markedly increased in aspirate smears and in most regions of the core. No blood transfusions had been given. Immunosuppressive treatment with prednisone was started, but the dog was euthanized 10 days later due to poor clinical progression.

Plasma cells in the bone marrow commonly contained coarse crystalline cytoplasmic inclusions that were green to brown in aspirate smears (Wright-Giemsa stain) and golden-brown in tissue sections (H&E stain) (Figure 1); the plasma cells otherwise lacked atypia. The granules were suggestive of iron, and Prussian blue positivity confirmed iron-rich inclusions. Histologic sections of liver collected at necropsy showed no increase in iron within hepatocytes or Kupffer cells.

Bone marrow siderotic plasma cells are rarely reported in nonalcoholic human patients, and the authors are unaware of reports in domestic mammals. In people, they have been associated mostly with conditions involving altered iron homeostasis and/or ineffective erythropoiesis: (1) systemic or marrow hemosiderosis from iron-loading anemias (e.g., megaloblastic anemia, sideroblastic anemias, refractory anemia with multilineage dysplasia, and pyruvate kinase-deficiency), recurrent transfusions, or hereditary hemochromatosis,² but not with iron accumulation from chronic inflammation,^{2, 3} and (2) marrow disease secondary to chronic alcoholism, which is associated with nutritional deficiencies and megaloblastic or sideroblastic anemias with ineffective erythropoiesis and low to high amounts of hemosiderin.^{2, 4} More rarely, plasma cell iron inclusions have been reported in people without clear evidence of altered iron homeostasis or ineffective erythropoiesis, for example, a minority of people with malignancies, including plasma cell myeloma.^{3, 5} Similar to most affected people, the dog in this report had ineffective erythropoiesis and increased marrow hemosiderin that suggests altered iron homeostasis, perhaps related to increased erythroferrone production.⁶ In people, transmission electron microscopy of siderotic plasma cells has shown increased cytosolic ferritin and iron accumulation in siderosomes,² perhaps from iron uptake mediated by cell membrane transferrin receptors.²

Siderotic plasma cells reflect disease, but they are currently of little diagnostic value in people and are of unknown diagnostic value in dogs. Recognizing the presence of these cells is the first step in determining if they have any clinical significance.

The authors declare they have no conflicts of interest.