CASES

Figures 9.60a,b Ultrasound images of abdominal masses present in a 9-year-old, spayed female Golden Retriever dog. (a) A 7.6 cm mass effect was noted in the cranial abdomen. It was challenging to determine if the mass effect was associated with the liver, spleen, or independent of these organs. (b) The liver was diffusely enlarged, and multiple small masses, some measuring up to 3.6 cm, were observed. (Courtesy Dr. Elizabeth Peters.)

Figures 9.61 Canine liver sample (Wright–Giemsa, 1,000? magnification).

Cytologic description

There are large cohesive clusters of hepatocytes present, which have an abundant amount of basophilic to pink granular cytoplasm, a centrally located round nucleus with finely stippled chromatin, and a single prominent nucleolus.

Cytologic interpretation

Likely regenerative nodule; rule out hepatocellular carcinoma.

Outcome

A follow-up on day 47 revealed that the biochemistry profile continued to improve but the mass was increasing in size on ultrasound. A surgical biopsy was elected.

Histology (Figure 9.62) revealed multifocal, 3 cm nodules composed of smaller nodules. The smaller nodules demonstrated a fibrous connective tissue capsule and bridging between portal triads (bridging fibrosis), atrophied hepatocytes, and serpiginous biliary ducts (biliary hyperplasia). Enlarged hepatic lobules lacked a central vein and had disorganized hepatic cords present, which were compressing adjacent parenchyma (hyperplastic nodule). Concurrently, these findings indicate hepatic cirrhosis (fibrosis and regeneration) and suggest massive hepatic necrosis. The FNA sample demonstrates the marked dysplasia that can occur with a strong regenerative effort.

Figure 9.62 Liver mass, histologic sections. Black arrow indicates thickened capsule. Black arrowhead indicates bridging fibrosis. Red arrow indicates lobular compression and atrophy. Asterisk indicates regenerative nodule (Mason-trichrome, 50? magnification). (Courtesy Dr. Arnon Gal.)

CASE 3

Signalment/history

Eleven-year-old, neutered male mixed-breed dog. The patient presented with a 3-week history of sudden onset seizure activity, which was refractory to medical management.

Physical examination

At presentation the dog appeared sedated to mentally inappropriate.

(Note: selected data from this case have been published previously [Moore et al., 2015].)

Figures 9.65a,b Histologic sections of the liver mass. (a) Note the typical neuroendocrine appearance of round cells in nests and packets surrounded by a fine connective tissue stroma (H&E, 200? magnification). (b) The neoplastic cells stained positive for insulin (anti-insulin, diaminobenzidine, hematoxylin counterstain, 200? magnification). A histologically similar insulin-positive mass was present in the pancreas. (Courtesy Dr. Caroline Chu.)

CASE 4

CASE material provided by Dr. Caitlyn Connor.

Signalment/history

Five-year-old, spayed female French bulldog. The patient was presented for a 3-week history of persistent vomiting and diarrhea, refractory to symptomatic therapy (maropitant, ondansetron, antibiotics).

Diagnostics

A CBC revealed a moderate macrocytic, normochromic nonregenerative anemia (Hct = 28.3%; reference interval [RI] = 42–60), moderate thrombocytopenia (platelets = 95 ? 10³/µL; RI = 226–424), and a moderate leukocytosis (WBC 37.3 ? 10³/µL; RI = 4.2–12.9) characterized by a moderate neutrophilia (segmented neutrophils = 24.99 ? 10³/µL; RI = 2.70–8.50) with a minimal regenerative left shift (band neutrophils = 0.373 ? 10³/µL; RI = 0.00–0.300) with minimal signs of toxicity noted, a moderate monocytosis (monocytes = 3.357 ? 10³/µL; RI = 0.100–1.00), minimal basophilia (basophils = 0.373 ? 10³/µL; RI = 0–0), and 17% ‘other cells’ (Figure 9.66).

Figure 9.66 Composite image of the nucleated cells found in the peripheral blood smear of a dog (modified Wright–Giemsa, 1,000? magnification).

A serum biochemistry profile displayed increased liver enzyme activity (ALT = 672 U/l; RI = 12–106; ALP = 446 U/l; RI = 13–102) and cholestasis (total bilirubin = 1.20 mg/dl; RI = 0.00–0.20), a mild hypoproteinemia (5.2 g/dl; RI= 5.4–7.1) characterized by a mild hypoalbuminemia (2.8 g/dl;RI = 3.3–4.2), a mild disproportionate hypochloridemia (98 mmol/l; RI = 106–114; sodium within reference interval at 144 mmol/l; RI = 143–150), a mild to moderate hypokalemia (3.3 mmol/l; RI = 3.7–5.1), mild hypocalcemia (9.2 mg/dl; RI = 9.5–11.2), and a mild hyperphosphatemia (6.4 mg/dl; RI= 2.7–5.2).

Thoracic radiographs did not show any significant findings. Abdominal radiographs exhibited hepatosplenomegaly, and abdominal ultrasound revealed hepatosplenomegaly with multiple splenic nodules, markedly enlarged jejunal lymph nodes, abdominal effusion, and a gastro-duodenal junction ulcer. Aspirates of the liver, spleen, jejunal lymph node, and abdominal fluid were submitted to a reference laboratory. Images from the liver aspirate are shown (Figure 9.67a–d).

Figures 9.67a–d Canine hepatic aspirate (modified Wright–Giemsa, a and b 500? magnification, c and d 1,000? magnification).

Cytologic description

Liver: there are many hepatocyte clusters. Hepatocytes are round to polygonal with mild to moderate amounts of deeply basophilic cytoplasm and a variable nuclear to cytoplasmic ratio. They occasionally contain blue–black granular material consistent with lipofuscin or other pigment, and many hepatocytes contain moderate amounts of distinct clear cytoplasmic vacuolization consistent with lipid. Nuclei are round to ovoid with finely reticular chromatin and one to rarely two distinct nucleoli. Anisocytosis and anisokaryosis are mild to moderate, and there are moderate numbers of binucleate cells. Few trinucleated cells are seen. There are many large discrete round cells with moderately expanded amounts of lightly basophilic cytoplasm and a round nucleus with smooth to stippled chromatin. Most of the cells have at least minimal amounts of fine to slightly coarse metachromatic cytoplasmic granulation. In most cells, this granulation is evenly distributed across the cytoplasm. In some cells, the granulation forms a small packet adjacent to the nucleus. The cells display moderate anisocytosis and anisokaryosis, with binucleation apparent and some cells having more distinct nucleoli. There are pigment-laden macrophages and few neutrophils seen in the background with cellular debris and proteinaceous fluid.

Blood smear: the leukocyte population appears moderately increased and is composed of mostly nondegenerate neutrophils with no appreciable toxic change. Monocytes appear morphologically normal and very few monocytes contain green pigment within the cytoplasm. Lymphocytes are predominantly small with a few intermediate-sized lymphocytes that are slightly smaller than the diameter of a neutrophil with deeply basophilic cytoplasm. Their nuclei are round with finely stippled chromatin and no discernible nucleoli. Eosinophils and basophils appear morphologically normal. The cells marked as ‘others’ are individualized mast cells. They contain moderate amounts of cytoplasm with variable numbers of fine to coarse deeply metachromatic granules distributed diffusely throughout the cytoplasm. Nuclei are centrally placed and ovoid to rarely irregular with fine stippled chromatin and no discernible nucleoli. No infectious etiologic agents are seen.

Cytologic interpretation

Liver: mast cell tumor; hepatocellular vacuolization consistent with lipid.

Peripheral blood: circulating mast cells due to mast cell neoplasia; mild macrocytic, nonregenerative anemia, suspect anemia of chronic disease; mild thrombocytopenia with evidence of thrombopoiesis.

Outcome

All sampled tissue (liver, spleen, lymph node, abdominal fluid, and peripheral blood) contained the neoplastic mast cells, providing evidence of disseminated disease (Figures 9.68). A primary tumor was not evident by imaging. Because of worsening clinical condition and poor prognosis, the patient was euthanized. Necropsy was not performed.

Figures 9.68a–d Spleen, jejunal lymph node, and abdominal fluid from a 5-year-old dog with mast cell neoplasia in the liver and peripheral blood. (a) The splenic aspirate had severe infiltration of neoplastic mast cells with variable amounts of metachromatic granules. Few small lymphocytes and neutrophils are present. (b) There were only scant lymphocytes present in the jejunal lymph node, but there were abundant neoplastic mast cells with variable amounts of metachromatic granules. (c) The neoplastic mast cells found in the other organs were present in the abdominal effusion and were more prominent than could be explained by peripheral blood contribution alone (modified Wright’s Giemsa, 1,000? magnification).

The primary tumor site was not identified in this patient. It is possible that the tumor originated in the liver or spleen or that these sites were metastasis from another location. Very low numbers of mast cells will be seen in healthy peripheral blood. The number and morphology of the circulating mast cells, and their morphologic similarity to the cells found in the liver, spleen, and jejunal lymph node, indicate circulating neoplastic mast cells. Circulating mast cells can be seen with hematogenous spread of visceral mast cell neoplasia and can also be seen with mast cell leukemia or mast cell neoplasia originating in the bone marrow; both of these conditions have a poor prognosis (Willman et al., 2021).

The hepatocellular atypia, lipid vacuolization, and the mixed hepatopathy appreciated on biochemistry were sequelae to the mast cell neoplastic infiltration of this organ rather than indicative of hepatic lipidosis. The nonregenerative anemia and thrombocytopenia are likely indirect sequelae to this disease process. The intracellular green pigment in the monocytes is nonspecific; however, it has been described in dogs with IMHA, post-blood transfusion, or even severe liver disease, which may be present in this case ( Gorup et al., 2017; Soos et al., 2019).

Acknowledgments

The author would like to thank Dr. Walter Hoffman for his assistance with this work.

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