Pathology Undergraduate & DVM Student Research Program

Diagnosis of Monocytic Leukemia in Dogs

Kristine K. Yu; Kenneth S. Latimer, DVM, PhD; Heather L. Tarpley, DVM; and Paula M. Krimer, DVM, DVSc

Undergraduate Honors Biology Program, The University of Georgia, Athens, GA 30602 (Yu) and Department of Pathology (Latimer, Tarpley, Krimer), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602

"Wizard" by Yvonne Sovereign Canine Art

Leukemia is a neoplasm of hematopoietic cells that originates within the bone marrow. Although the term "leukemia" means "white blood," this neoplastic condition can involve leukocytes, erythrocytes, megakaryocytes and platelets, or mast cells singly or in combination. All of these cells originate from a common pluripotential stem cell. The three main types of leukocytes are granulocytes (including neutrophils, eosinophils, and basophils), monocytes, and lymphocytes. Neutrophils and monocytes are derived from a common bipotential precursor cell, a colony forming unit that produces granulocytes (neutrophils) and monocytes (CFU-GM, Fig 1). Leukemic transformation of the bipotential CFU-GM precursor cell can result in three forms of leukemia that can produce neutrophils, monocytes, or a combination of both cell types. These types of neoplasia are called granulocytic leukemia, monocytic leukemia, and myelomonocytic leumekia, respectively.

Figure 1. Overview of hematopoiesis. Neutrophils and monocytes are derived from a bipotential stem cell designated granulocyte-macrophage colony forming unit (CFU-GM).

Clinical signs of monocytic leukemia are nonspecific and include fever, lethargy, affects weight loss, anorexia, and occasional changes in skin texture. Physical examination also may disclose enlarged tonsils, lymphadenopathy, hepatosplenomegaly, and hemorrhage. Laboratory findings include mild to moderate anemia (~26-34%), leukocytosis, and moncoytosis that may range from mild to extreme (5,000 to > 800,000 monocytes /µl of blood). With higher leukocyte counts, monocytes and monoblasts may account for > 90% of the leukocyte differential count.

Diagnosis of monocytic leukemia is usually based upon the complete blood cell count and examination of cellular morphology on Romanowsky-stained blood and bone marrow smears (Fig. 2). Cellular lineage usually can be identified easily in chronic monocytic leukemia; however, acute monocytic leukemia is more difficult to diagnose. In acute monocytic leukemia, the neoplastic cells are undifferentiated blasts that often resemble lymphoblasts (Fig. 3). Definitive diagnosis of acute monocytic leukemia in dogs ultimately is based upon cytochemistry, immunocytochemistry, and transmission electron microscopy.

Figure 2. Chronic monocytic leukemia in a dog. These cells are easily recognized as monocytes (Wright-Leishman stain). Figure 3. Acute monocytic leukemia in a dog. These cells are poorly differentiatted and resemble lymphocytes (Wright-Leishman stain).

A panel of cytochemical stains is applied to blood and bone marrow smears to determine the lineage of the leukemic cells. Monocytes usually exhibit fluoride sensitive alpha naphthyl acetate esterase or alpha naphthyl butyrate esterase activities. Neoplastic monocytes usually lack alkaline phosphatase, myeloperoxidase, and chloroacetate esterase activities (Fig. 4). Antibodies to cell membrane antigens may be used in conjunction with flow cytometry to characterize leukemic cell populations.

Figure 4. Monoblasts have brown cytoplasm indicating reactivity for alpha naphthyl actetate esterase activity (Alpha naphthyl actetate esterase technique with fast green counterstain).

Transmission electron microscopy can be used to evaluate cytochemical staining reactions and identify organelles ultrastructurally. Typical organelles of monocytes include lysosomes, a few mitochondria, and microfilament bundles. Neoplastic cells may have a smooth plasma membrane or scattered pseudopodia along the surface of the cell membrane (Fig. 5 and Fig. 6). Cytoplasmic vacuoles also may be present.

Figure 5. Transmission electron micrograph of a neoplastic monocyte with pseudopodia, few mitochondria, and infrequent lysosomes (osmiun tetroxide and lead citrate staining).

Figure 6. Transmission electron micrograph of a neoplastic monocyte. Microfilament bundles (arrowheads) are present between nuclear lobes (osmiun tetroxide and lead citrate staining)

Diagnosis of monocytic leukemia may require examination of Romanowsky-stained blood and bone marrow smears, cytochemical staining, and transmission electron microscopy. Precise identification of cellular lineage is necessary if treatment of leukemia will be attempted.

References

Grindem CB: Ultrastructural morphology of leukemic cells from 14 dogs. Vet Pathol 22:456-4621985.

Grindem CB: Cytochemical reactions in cells from leukemic dogs. Vet Pathol 23:103-109, 1986.

Latimer KS, Dykstra MJ: Acute monocytic leukemia in a dog. J Am Vet Med Assoc 184:852-854, 1984.

Mackey LJ: Monocytic leukemia in the dog. Vet Rec 96:27-30, 1975.

Tolle DV, Seed TM, Fritz TE, Lombard LS, Poole CM, Norris WP: Acute monocytic leukemia in an irradiated beagle. Vet Pathol 16:243-254, 1979.

 

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