Section 5: Hematopoietic Neoplasia Overview Lymphoid Leukemia Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia T-Cell Large Granular Lymphocytic Leukemia Acute Myeloid Leukemia Acute Undifferentiated Leukemia Acute Myeloblastic Leukemia Acute Promyelocytic Leukemia Acute Myelomonocytic Leukemia Acute Monocytic Leukemia Acute Erythroleukemia Acute Megakaryoblastic Leukemia Chronic Myeloid Leukemia Chronic Granulocytic Leukemia Chronic Monocytic Leukemia Chronic Myelomonocytic Leukemia Polycythemia Vera Essential Thrombocythemia Mitotic Figures Overview Leukemia is defined as a clonal proliferation of neoplastic cells originating in bone marrow. Leukemia of every peripheral blood cell type has been identified in dogs and cats. Lymphoid leukemia (both acute and chronic forms) is common in dogs and cats, whereas leukemias of the other cell lines are quite uncommon. Diagnosis of leukemia is based on clinical presentation (clinical signs and physical examination), and laboratory data, including complete blood count (CBC) and serum chemistry analysis. The findings of large numbers of neoplastic cells on CBC and blood smear microscopic evaluation are one important part of the diagnosis and classification of the various leukemias. Definitive diagnosis may often require bone marrow evaluation. Many different leukemia classification schemes have been proposed and utilized. Various schemes are based on a mix of information such as clinical behavior (response to therapy, survival time), cellular morphology (microscopic evaluation of the neoplastic cells), histopathology (neoplastic pattern on tissue biopsy), topography (extent of neoplastic involvement), phenotype (genetic expression), and genotype (genetic characteristics and aberrations) of the neoplastic cell population. Although blood smear evaluation remains an important part of diagnosis and classification of leukemias, it is important to recognize that morphology alone is not sufficient to classify various leukemias. This is especially true with the acute forms of leukemia, as blasts of various lineages may appear morphologically identical. Two large categories of leukemia exist: (1) lymphoid leukemias and (2) myeloid (nonlymphoid) leukemias, with acute and chronic forms of each category. Acute leukemias are composed of blast cells. This type of leukemia manifests acutely and is aggressive, often associated with large numbers of circulating blasts, peripheral blood cytopenias, occasional secondary organ infiltration, and a poorer prognosis compared with that for chronic leukemias. With regard to acute leukemias, identification of the lineage of the blast cell population may be difficult, especially if it is solely based on light-microscopic morphologic features with routine hematologic stains. Blast cells may sometimes have distinct features to suggest phenotype; however, most appear similar microscopically, and further tests are needed to identify ontogeny. Such tests aiding in differentiation may include cytochemical staining using enzymes and immunocytochemistry or flow cytometry, which utilize labeled antibodies targeted against specified antigens found in various cell lines (immunophenotyping). Furthermore, clonality tests are available for identifying lymphoid leukemias, to assess whether a population of lymphoid cells are clonal in origin (suggestive of neoplasia) or nonclonal (suggestive of inflammation or reactivity). Identification of genetic abnormalities (cytogenetics) is increasingly playing a role in the classification of leukemias in veterinary medicine. In contrast to acute leukemias, chronic leukemias develop more slowly, are not often associated with cytopenias until the late stage of disease, often do not have organ involvement, and are associated with a more favorable prognosis. The neoplastic cell population in chronic leukemias comprises mature, well-differentiated cells that are often morphologically identical to normal blood leukocytes. Thus, the mature morphology of the neoplastic cells may make it very difficult to distinguish leukemia from inflammatory processes. Differentiation is based on ruling out sources of infection, inflammation, or immunostimulation and continued monitoring of the CBC over time to document the persistence, and increasing numbers, of one type of leukocyte. A brief overview of the different types of leukemias in dogs and cats is presented in this chapter, with an emphasis on morphologic features. Lymphoid Leukemia Acute Lymphoblastic Leukemia Distinctive Features: Acute lymphoblastic leukemia (ALL) is a neoplastic proliferation of lymphoblasts and may be either B-cell or T-cell phenotype. Lymphoblasts are large cells, often 1.5 to 2 times the diameter of neutrophils. Lymphoblasts contain slight to moderate amounts of basophilic cytoplasm, a round to oval eccentrically placed nucleus, stippled to slightly coarse nuclear chromatin, and often either faint or, more commonly, prominent nucleoli. Nucleoli are typically singular, but occasionally, two nucleoli may be present. Diagnostic Significance: Lymphoblasts are rarely seen in the peripheral blood of normal dogs and cats. Occasional lymphoblasts may be seen in peripheral blood with strong immune stimulation. Low to high numbers of lymphoblasts may be seen in peripheral blood with lymphoblastic leukemia. Classic CBC findings with ALL include large numbers of circulating blasts and, often, one or multiple cytopenias. Next Steps: Light microscopy alone cannot reliably distinguish T-cell ALL from B-cell ALL, nor can it reliably distinguish lymphoblasts from myeloblasts or monoblasts. Other methods such as immunocytochemistry and flow cytometry are needed to define exact phenotype. B-cell leukemia is associated with a more favorable prognosis compared with T-cell leukemia. Low to occasional to moderate numbers of circulating lymphoblasts may be seen with stage V lymphoma, indicating neoplastic seeding of bone marrow and the subsequent leukemic phase. Distinguishing stage V lymphoma from late stage lymphoid leukemia may be difficult. Determining the location of the bulk of neoplastic involvement (marrow or blood versus solid tissue) may be used to distinguish the conditions. Finding low to high numbers of blasts in peripheral blood warrants assessment for involvement of lymphoreticular organs for staging purposes. Plate 5-1 Acute Lymphoblastic Leukemia Next Topic Plate 5-1a Plate 5-1b Plate 5-1c Plate 5-1d Plate 5-1e Plate 5-1f Plate 5-1g Plate 5-1h Plate 5-1i Plate 5-1j Plate 5-1a Return to text. Return to image plate. Plate 5-1b Return to text. Return to image plate. Plate 5-1c Return to text. Return to image plate. Plate 5-1d Return to text. Return to image plate. Plate 5-1e Return to text. Return to image plate. Plate 5-1f Return to text. Return to image plate. Plate 5-1g Return to text. Return to image plate. Plate 5-1h Return to text. Return to image plate. Plate 5-1i Return to text. Return to image plate. Plate 5-1j Return to text. Return to image plate. Chronic Lymphocytic Leukemia Distinctive Features: Chronic lymphocytic leukemia (CLL) is a neoplastic proliferation of small, mature lymphocytes. Morphology is identical to that of nonneoplastic mature lymphocytes. The lymphocytosis in CLL may be mild in early stages and marked in later stages. Cytopenias are uncommon and typically only seen when the neoplastic cells are present in very high numbers. Diagnostic Significance: CLL is most often a leukemia found in older dogs and cats. When a mild to moderate lymphocytosis is present, distinguishing it from a reactive population of lymphocytes secondary to immunostimulation may be difficult and relies on monitoring of the CBC over time (persistent lymphocytosis, often with a slowly progressive increase in numbers). Immunophenotypic analysis and documentation of a monoclonal population may also lend support to the diagnosis of leukemia. In addition, clonality testing is also available to help identify clonal populations of lymphocytes. It is important to recognize that clonality by itself is not diagnostic of neoplasia. As an example, clonal populations of T lymphocytes have been identified in dogs with chronic ehrlichiosis. Next Steps: As for ALL, distinguishing between B-cell and T-cell phenotypes is not possible with light microscopy alone, and further techniques are required. When CLL is diagnosed, assessment for involvement of the lymphoreticular organs is advised to further stage the disease. A diagnosis of CLL warrants monitoring of the CBC, despite treatment, as evolution into a blast crisis may occur, culminating in an acute leukemia. Plate 5-2 Chronic Lymphocytic Leukemia Next Topic Plate 5-2a Plate 5-2b Plate 5-2c Plate 5-2d Plate 5-2e Plate 5-2f Plate 5-2g Plate 5-2h Plate 5-2i Plate 5-2j Plate 5-2a Return to text. Return to image plate. Plate 5-2b Return to text. Return to image plate. Plate 5-2c Return to text. Return to image plate. Plate 5-2d Return to text. Return to image plate. Plate 5-2e Return to text. Return to image plate. Plate 5-2f Return to text. Return to image plate. Plate 5-2g Return to text. Return to image plate. Plate 5-2h Return to text. Return to image plate. Plate 5-2i Return to text. Return to image plate. Plate 5-2j Return to text. Return to image plate. T-Cell Large Granular Lymphocytic Leukemia Distinctive Features: T-cell large granular lymphocytic leukemia (T-cell LGL leukemia) is composed of large, immature T lymphocytes, with variable numbers of round to irregular, variably sized, magenta-staining cytoplasmic granules. Diagnostic Significance: Low numbers of nonneoplastic circulating granular lymphocytes may be seen in dogs and cats secondary to immunostimulation. In particular, low to moderate numbers of granular lymphocytes may be seen in dogs, with or without a mild lymphocytosis and with ehrlichiosis. Thus, as with CLL, ruling out etiologies of immunostimulation and monitoring of the CBC over time are needed to help confirm a leukemic process. Next Steps: As for all of the lymphoid leukemias, assessment for lymphoreticular organ infiltration is suggested for staging. Although commonly referred to as lymphocytic leukemia of granular lymphocytes, in dogs, this disorder actually arises in the spleen rather than in bone marrow. Plate 5-3 T-Cell Large Granular Lymphocytic Leukemia Next Topic Plate 5-3a Plate 5-3b Plate 5-3c Plate 5-3d Plate 5-3e Plate 5-3f Plate 5-3g Plate 5-3h Plate 5-3a Return to text. Return to image plate. Plate 5-3b Return to text. Return to image plate. Plate 5-3c Return to text. Return to image plate. Plate 5-3d Return to text. Return to image plate. Plate 5-3e Return to text. Return to image plate.< div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: 6: Extracellular Organisms 4: Platelets 1: General Assessment 3: White Blood Cells Stay updated, free articles. 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Section 5: Hematopoietic Neoplasia Overview Lymphoid Leukemia Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia T-Cell Large Granular Lymphocytic Leukemia Acute Myeloid Leukemia Acute Undifferentiated Leukemia Acute Myeloblastic Leukemia Acute Promyelocytic Leukemia Acute Myelomonocytic Leukemia Acute Monocytic Leukemia Acute Erythroleukemia Acute Megakaryoblastic Leukemia Chronic Myeloid Leukemia Chronic Granulocytic Leukemia Chronic Monocytic Leukemia Chronic Myelomonocytic Leukemia Polycythemia Vera Essential Thrombocythemia Mitotic Figures Overview Leukemia is defined as a clonal proliferation of neoplastic cells originating in bone marrow. Leukemia of every peripheral blood cell type has been identified in dogs and cats. Lymphoid leukemia (both acute and chronic forms) is common in dogs and cats, whereas leukemias of the other cell lines are quite uncommon. Diagnosis of leukemia is based on clinical presentation (clinical signs and physical examination), and laboratory data, including complete blood count (CBC) and serum chemistry analysis. The findings of large numbers of neoplastic cells on CBC and blood smear microscopic evaluation are one important part of the diagnosis and classification of the various leukemias. Definitive diagnosis may often require bone marrow evaluation. Many different leukemia classification schemes have been proposed and utilized. Various schemes are based on a mix of information such as clinical behavior (response to therapy, survival time), cellular morphology (microscopic evaluation of the neoplastic cells), histopathology (neoplastic pattern on tissue biopsy), topography (extent of neoplastic involvement), phenotype (genetic expression), and genotype (genetic characteristics and aberrations) of the neoplastic cell population. Although blood smear evaluation remains an important part of diagnosis and classification of leukemias, it is important to recognize that morphology alone is not sufficient to classify various leukemias. This is especially true with the acute forms of leukemia, as blasts of various lineages may appear morphologically identical. Two large categories of leukemia exist: (1) lymphoid leukemias and (2) myeloid (nonlymphoid) leukemias, with acute and chronic forms of each category. Acute leukemias are composed of blast cells. This type of leukemia manifests acutely and is aggressive, often associated with large numbers of circulating blasts, peripheral blood cytopenias, occasional secondary organ infiltration, and a poorer prognosis compared with that for chronic leukemias. With regard to acute leukemias, identification of the lineage of the blast cell population may be difficult, especially if it is solely based on light-microscopic morphologic features with routine hematologic stains. Blast cells may sometimes have distinct features to suggest phenotype; however, most appear similar microscopically, and further tests are needed to identify ontogeny. Such tests aiding in differentiation may include cytochemical staining using enzymes and immunocytochemistry or flow cytometry, which utilize labeled antibodies targeted against specified antigens found in various cell lines (immunophenotyping). Furthermore, clonality tests are available for identifying lymphoid leukemias, to assess whether a population of lymphoid cells are clonal in origin (suggestive of neoplasia) or nonclonal (suggestive of inflammation or reactivity). Identification of genetic abnormalities (cytogenetics) is increasingly playing a role in the classification of leukemias in veterinary medicine. In contrast to acute leukemias, chronic leukemias develop more slowly, are not often associated with cytopenias until the late stage of disease, often do not have organ involvement, and are associated with a more favorable prognosis. The neoplastic cell population in chronic leukemias comprises mature, well-differentiated cells that are often morphologically identical to normal blood leukocytes. Thus, the mature morphology of the neoplastic cells may make it very difficult to distinguish leukemia from inflammatory processes. Differentiation is based on ruling out sources of infection, inflammation, or immunostimulation and continued monitoring of the CBC over time to document the persistence, and increasing numbers, of one type of leukocyte. A brief overview of the different types of leukemias in dogs and cats is presented in this chapter, with an emphasis on morphologic features. Lymphoid Leukemia Acute Lymphoblastic Leukemia Distinctive Features: Acute lymphoblastic leukemia (ALL) is a neoplastic proliferation of lymphoblasts and may be either B-cell or T-cell phenotype. Lymphoblasts are large cells, often 1.5 to 2 times the diameter of neutrophils. Lymphoblasts contain slight to moderate amounts of basophilic cytoplasm, a round to oval eccentrically placed nucleus, stippled to slightly coarse nuclear chromatin, and often either faint or, more commonly, prominent nucleoli. Nucleoli are typically singular, but occasionally, two nucleoli may be present. Diagnostic Significance: Lymphoblasts are rarely seen in the peripheral blood of normal dogs and cats. Occasional lymphoblasts may be seen in peripheral blood with strong immune stimulation. Low to high numbers of lymphoblasts may be seen in peripheral blood with lymphoblastic leukemia. Classic CBC findings with ALL include large numbers of circulating blasts and, often, one or multiple cytopenias. Next Steps: Light microscopy alone cannot reliably distinguish T-cell ALL from B-cell ALL, nor can it reliably distinguish lymphoblasts from myeloblasts or monoblasts. Other methods such as immunocytochemistry and flow cytometry are needed to define exact phenotype. B-cell leukemia is associated with a more favorable prognosis compared with T-cell leukemia. Low to occasional to moderate numbers of circulating lymphoblasts may be seen with stage V lymphoma, indicating neoplastic seeding of bone marrow and the subsequent leukemic phase. Distinguishing stage V lymphoma from late stage lymphoid leukemia may be difficult. Determining the location of the bulk of neoplastic involvement (marrow or blood versus solid tissue) may be used to distinguish the conditions. Finding low to high numbers of blasts in peripheral blood warrants assessment for involvement of lymphoreticular organs for staging purposes. Plate 5-1 Acute Lymphoblastic Leukemia Next Topic Plate 5-1a Plate 5-1b Plate 5-1c Plate 5-1d Plate 5-1e Plate 5-1f Plate 5-1g Plate 5-1h Plate 5-1i Plate 5-1j Plate 5-1a Return to text. Return to image plate. Plate 5-1b Return to text. Return to image plate. Plate 5-1c Return to text. Return to image plate. Plate 5-1d Return to text. Return to image plate. Plate 5-1e Return to text. Return to image plate. Plate 5-1f Return to text. Return to image plate. Plate 5-1g Return to text. Return to image plate. Plate 5-1h Return to text. Return to image plate. Plate 5-1i Return to text. Return to image plate. Plate 5-1j Return to text. Return to image plate. Chronic Lymphocytic Leukemia Distinctive Features: Chronic lymphocytic leukemia (CLL) is a neoplastic proliferation of small, mature lymphocytes. Morphology is identical to that of nonneoplastic mature lymphocytes. The lymphocytosis in CLL may be mild in early stages and marked in later stages. Cytopenias are uncommon and typically only seen when the neoplastic cells are present in very high numbers. Diagnostic Significance: CLL is most often a leukemia found in older dogs and cats. When a mild to moderate lymphocytosis is present, distinguishing it from a reactive population of lymphocytes secondary to immunostimulation may be difficult and relies on monitoring of the CBC over time (persistent lymphocytosis, often with a slowly progressive increase in numbers). Immunophenotypic analysis and documentation of a monoclonal population may also lend support to the diagnosis of leukemia. In addition, clonality testing is also available to help identify clonal populations of lymphocytes. It is important to recognize that clonality by itself is not diagnostic of neoplasia. As an example, clonal populations of T lymphocytes have been identified in dogs with chronic ehrlichiosis. Next Steps: As for ALL, distinguishing between B-cell and T-cell phenotypes is not possible with light microscopy alone, and further techniques are required. When CLL is diagnosed, assessment for involvement of the lymphoreticular organs is advised to further stage the disease. A diagnosis of CLL warrants monitoring of the CBC, despite treatment, as evolution into a blast crisis may occur, culminating in an acute leukemia. Plate 5-2 Chronic Lymphocytic Leukemia Next Topic Plate 5-2a Plate 5-2b Plate 5-2c Plate 5-2d Plate 5-2e Plate 5-2f Plate 5-2g Plate 5-2h Plate 5-2i Plate 5-2j Plate 5-2a Return to text. Return to image plate. Plate 5-2b Return to text. Return to image plate. Plate 5-2c Return to text. Return to image plate. Plate 5-2d Return to text. Return to image plate. Plate 5-2e Return to text. Return to image plate. Plate 5-2f Return to text. Return to image plate. Plate 5-2g Return to text. Return to image plate. Plate 5-2h Return to text. Return to image plate. Plate 5-2i Return to text. Return to image plate. Plate 5-2j Return to text. Return to image plate. T-Cell Large Granular Lymphocytic Leukemia Distinctive Features: T-cell large granular lymphocytic leukemia (T-cell LGL leukemia) is composed of large, immature T lymphocytes, with variable numbers of round to irregular, variably sized, magenta-staining cytoplasmic granules. Diagnostic Significance: Low numbers of nonneoplastic circulating granular lymphocytes may be seen in dogs and cats secondary to immunostimulation. In particular, low to moderate numbers of granular lymphocytes may be seen in dogs, with or without a mild lymphocytosis and with ehrlichiosis. Thus, as with CLL, ruling out etiologies of immunostimulation and monitoring of the CBC over time are needed to help confirm a leukemic process. Next Steps: As for all of the lymphoid leukemias, assessment for lymphoreticular organ infiltration is suggested for staging. Although commonly referred to as lymphocytic leukemia of granular lymphocytes, in dogs, this disorder actually arises in the spleen rather than in bone marrow. Plate 5-3 T-Cell Large Granular Lymphocytic Leukemia Next Topic Plate 5-3a Plate 5-3b Plate 5-3c Plate 5-3d Plate 5-3e Plate 5-3f Plate 5-3g Plate 5-3h Plate 5-3a Return to text. Return to image plate. Plate 5-3b Return to text. Return to image plate. Plate 5-3c Return to text. Return to image plate. Plate 5-3d Return to text. Return to image plate. Plate 5-3e Return to text. Return to image plate.< div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: 6: Extracellular Organisms 4: Platelets 1: General Assessment 3: White Blood Cells Stay updated, free articles. 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