Page 757 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition
P. 757

CHAPTER 33  Hematopoietic Tumors  735


           in all bone marrow cells, signifying a lesion at the level of an   PV, should be ruled out, and importantly, there should be no
           early multipotent stem cell. Typically, these individuals have   primary disorders associated with reactive thrombocytosis, 710
                                                                 including inflammation, hemolytic anemia, iron deficiency ane-
           a chromosomal translocation, resulting in the Philadelphia
  VetBooks.ir  chromosome or BCR–ABL translocation between chromo-  mia, malignancies, recovery from severe hemorrhage, rebound
                        699
                            The analogous chromosomes in dogs are
           somes 9 and 22.
                                                                 from immune-mediated  thrombocytopenia, and splenectomy.
           chromosomes 9 and 26, and BCR–ABL translocation, termed   In addition, certain drugs such as vincristine can induce throm-
           the “Raleigh chromosome,” has been reported in several cases   bocytosis. ET has been recognized in dogs. 642,711–714  In one dog,
           of CML in dogs. 614,627,700,701   Variants of CML are chronic   the platelet count exceeded 4 million/μL and bizarre giant forms
           myelomonocytic leukemia and chronic monocytic leukemia   with abnormal granulation were present. The bone marrow con-
           (CMoL). 702–704  CMoL has also been associated with BCR–ABL   tained increased numbers of megakaryocytes and megakaryo-
           translocation in the dog. 702  These diagnoses are made based on   blasts, but circulating blast cells were not seen. Other findings
           the percentage of monocytes in the leukemic cell population.   included splenomegaly, GI bleeding, and increased numbers of
           An infrequent myeloproliferative neoplasm, atypical chronic   circulating basophils. Causes of secondary or reactive throm-
           myeloid leukemia, has been reported in a dog and had features   bocytosis were ruled out. 713  Basophilia was also reported in a
           of both myelodysplastic syndrome and chronic leukemia. 700  In   more recent case. 711  In another dog, ET was diagnosed and then
           this dog, BCR–ABL translocation was present in fewer than   progressed to CML. 642  In some cases reported in the literature
           10% of cells, considered a negative finding.          as ET, the dogs had microcytic hypochromic anemias. Because
             In addition to accumulating in bone marrow and periph-  iron deficiency anemia is associated with reactive or secondary
           eral blood, leukemic cells also are found in the red pulp of   thrombocytosis, care must be taken to rule out this disorder.
           the spleen, the periportal and sinusoidal areas of the liver,   However, spurious microcytosis may be reported if a dog has
           and sometimes lymph nodes. Other organs, such as the kid-  many giant platelets that are counted by some analyzers as small
           ney, heart, and lung, are less commonly affected. In addition,   RBCs. 712  Microscopic review of the blood film may be helpful
           extramedullary hematopoiesis may be present in the liver and   in these cases. 
           spleen. Death is usually due to complications of infection or
           hemorrhage secondary to neutrophil dysfunction and throm-
           bocytopenia, respectively. In some cases, CML may terminate   Other Bone Marrow Disorders
           in “blast crisis,” in which there is a transformation from a   Myelofibrosis
           predominance of well-differentiated granulocytes to excessive
           numbers of poorly differentiated blast cells in peripheral blood   Primary myelofibrosis has been reported only rarely in dogs,
           and bone marrow. This phenomenon is well documented in the   and myelofibrosis is more typically a secondary, or reactive, pro-
           dog. 693,696,698                                      cess. 715,716  In humans, myelofibrosis is characterized by collagen
                                                                 deposition in bone marrow and increased numbers of megakaryo-
           Basophilic and Eosinophilic Leukemia                  cytes and granulocytic precursors, many of which exhibit mor-
                                                                 phologic abnormalities. In fact, breakdown of intramedullary
           Basophilic leukemia, although rare, has been reported in dogs and   megakaryocytes and subsequent release of factors that promote
           is characterized by an increased WBC count with a high propor-  fibroblast proliferation or inhibit collagen breakdown may be the
           tion of basophils in peripheral blood and bone marrow. 705–707    underlying pathogenesis of the fibrosis. 717  Focal osteosclerosis is
           Hepatosplenomegaly,  lymphadenopathy,  and  thrombocytosis   sometimes  present. Anemia,  thrombocytopenia,  splenomegaly,
           may be present. All the dogs have been anemic. Basophilic leu-  and myeloid metaplasia (production of hematopoietic cells out-
           kemia should be distinguished from mast cell leukemia (masto-  side the bone marrow) are consistent features.
           cytosis). Whether dogs develop eosinophilic leukemia remains in   In  dogs,  myelofibrosis  occurs  secondary  to  MPDs,  radia-
           question. Reported cases have had high blood eosinophil counts   tion damage, and congenital hemolytic anemias. 718–721  In
           and eosinophilic infiltrates in organs. 708,709  One dog responded   some cases, the inciting cause is unknown (idiopathic myelo-
           well to treatment with corticosteroids. The distinction between   fibrosis). There may be concurrent marrow necrosis in cases of
           neoplastic proliferation of eosinophils and idiopathic hypereosin-  ehrlichiosis, septicemia, or drug toxicity (estrogens, cephalo-
           ophilic syndrome remains elusive. Nonmyeloproliferative disor-  sporins), and there is speculation that fibroblasts proliferate in
           ders associated with eosinophilia such as parasitism, skin diseases,   response to release of inflammatory mediators associated with
           or diseases of the respiratory and GI tracts should be considered   the necrosis. 715  Myeloid metaplasia has been reported to occur
           first in an animal with eosinophilia. One distinguishing feature   in the liver, spleen, and lung. 721  Extramedullary hematopoiesis
           should be clonality, with reactive eosinophilia comprising poly-  is ineffective in preventing or correcting the pancytopenia that
           clonal cells and the neoplastic condition arising from a single   eventually develops. 
           clone. As clonality assays become more available, this discrepancy
           may be resolved.                                      Myelodysplastic Syndrome

           Essential Thrombocythemia                             Dysfunction of the hematopoietic system can be manifested by a
                                                                 variety of abnormalities that constitute myelodysplastic syndrome
           In humans, ET, or primary thrombocytosis, is characterized by   (MDS). In dogs, in which the syndrome is rare, there usually are
           platelet counts that are persistently greater than 600,000/μL.   cytopenias in two or three lines in the peripheral blood (anemia,
           There are no blast cells in circulation and marked megakaryocytic   neutropenia, and/or thrombocytopenia). Other blood abnormali-
           hyperplasia of the bone marrow without myelofibrosis is pres-  ties can include macrocytic erythrocytes and metarubricytosis.
           ent. Thrombosis and bleeding are the most common sequelae,   The bone marrow is typically normocellular or hypercellular, and
           and most patients have splenomegaly. Other MPDs, especially   dysplastic changes are evident in several cell lines. If blast cells are
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