Copper

Copper accumulation can be detected in Romanowsky-stained cytologic preparations as a blue–green to gray cytoplasmic crystalline material (Figure 9.18a). Copper content is not always readily apparent by Romanowsky staining but can be highlighted using rubeanic acid or rhodanine stains (Moore et al., 2016; Figures 9.18b, c).

Hepatic copper accumulation has been associated with chronic hepatitis and altered excretion during cholestasis in both canine and feline patients (Whittemore et al., 2012; Hurwitz et al., 2014; Cedeño et al., 2016; Eulenberg et al., 2018). Data also suggest that copper may induce chronic hepatitis and contribute to the development of hepatocellular carcinoma (Harro et al., 2019). A genetic copper hepatopathy has been demonstrated in Bedlington Terriers, Labrador Retrievers, and other dogs (Hoffmann, 2009). The amount of copper accumulated in the liver of Labrador Retrievers with primary copper hepatopathy is correlated with dietary copper content (Fieten et al., 2012). Primary copper-associated hepatopathy was seen in young cats without cholestasis, suggesting genetic or environmental causes in the cat (Hurwitz et al., 2014).

Hemosiderin/hematoidin

Hemosiderin and its iron-free homologue, hematoidin, are present in patients with increased erythrocyte turnover (hemolytic anemia or recent transfusion) and portosystemic shunts.

Figures 9.17a,b Canine liver sample. (a) The hepatocytes from this dog have blue to blue–green cytoplasmic material, most consistent with lipofuscin. A platelet clump is also noted in the lower center of the image (Wright–Giemsa, 1,000? magnification). (b) Neutrophils within the hepatocyte clumps, a feature commonly used to aid the diagnosis of suppurative hepatitis, are not found. The neutrophil count in this liver aspirate is higher than that of peripheral blood and myeloid precursors are not found (helping to exclude peripheral blood contamination and extramedullary hematopoiesis, respectively) (Wright–Giemsa, 500? magnification). This patient was given a diagnosis of mild suppurative hepatitis.

Figures 9.18a–c Seven-year-old Labrador Retriever. The patient had normal serum liver enzyme values but hypoechoic areas on ultrasound evaluation of the liver. (a) Hepatocytes with dark blue–black and pale blue–green to blue–gray cytoplasmic granules were noted (Wright–Giemsa, 1,000? magnification). (b) The blue–green to blue–gray granules stained orange–brown after rhodanine staining, consistent with copper.

Figures 9.19a,b Nine-year-old Terrier-cross dog with a 6-month history of weight loss and recently elevated liver enzymes. (a) Clusters of hepatocytes are present in the upper left corner. There is a mixed lymphoid population with small lymphocytes predominant, suggestive of lymphocytic inflammation. The blue–black granules are suggestive of hemosiderin. A pigment-laden macrophage is present in the lower right corner (Wright–Giemsa, 500? magnification). (b) Prussian blue stain confirms the presence of iron and helps demonstrate the amount of hemosiderin that can be present in liver samples. Hemosiderin likely accumulated secondary to inflammation. Inset image is from the control slide; note the blue-staining iron within this macrophage (Wright–Giemsa, 500? magnification). (Same dog as in Figure 9.28.)