An Overview of Feline Erythremic Myelosis
M. K. Tolbert, DVM; H. M. Brown, DVM; K. S. Latimer, DVM, PhD, DACVP
Class of 2006 (Tolbert) and Department of Pathology (Brown, Latimer), College of Veterinary Medicine, University of Georgia, Athens, GA, 30602-7388
Introduction
Erythremic myelosis is a myeloproliferative disorder characterized by the presence of severe nonregenerative anemia with a neoplastic proliferation of immature, nucleated erythrocytes. Peripheral blood smears reveal variable numbers of metarubricytes, rubricytes, and rubriblasts with markedly decreased mature erythrocytes (Figures 1 and 2). The metarubricytosis suggests a regenerative response to the anemia; however, lack of significant numbers of circulating polychromatophilic erythrocytes (in Romanowsky- stained blood smears) or reticulocytes (in new methylene blue-stained blood smears) classifies the anemia as nonregenerative. In erythremic myelosis, the neoplastic proliferation of erythroid precursors originates in the bone marrow and, as such, is currently categorized under the veterinary-adapted guidelines of the French-American British (FAB) cooperative group as a either a myelodysplastic syndrome with erythroid predominance (MDS-Er) or an acute myelogenous leukemia (M6-Er: Erythroleukemia with erythroid predominance).1
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Figure 1. Immature erythrocytes in the blood of a cat with erythremic myelosis. Note the metarubricytes (arrowheads), rubricytes (arrows), and rubriblasts (asterisks), and a relative lack of polychromatophils. Wright-Leishman stain. |
Figure 2. Rubriblasts in the blood of a cat with erythremic myelosis. Notice the prominent nucleoli (arrows). Wright-Leishman stain. |
Pathogenesis
The pathogenesis of erythremic myelosis is not completely understood. Feline erythremic myelosis is thought to be caused by a mutation in the nucleic acid synthesis of precursor erythroid cells within the bone marrow, resulting in maturation arrest of the erythrocytes and a marked non-regenerative anemia.2,8 Immature erythroid cells are then released from the bone marrow into circulation in a frustrated effort to meet the body’s demand for erythrocyte production to reverse the effects of anemia. Cats infected with feline leukemia virus (FeLV) are predisposed to develop erythremic myelosis and other myeloid and lymphoid neoplasms. Studies suggest that FeLV subgroup C has a direct action on early erythroid precursors and FeLV-associated erythremic myelosis may result from this primary viral infection which produces a mutation resulting in the clonal proliferation of erythroid precursor cells.2,3 As with other myeloproliferative diseases, erythremic myelosis may evolve from one morphological form into another. Progression to acute leukemia is common and may occur within weeks to months after the initial diagnosis of myelodysplasia.4 Cats with erythremic myelosis also may undergo blast transformation to erythroleukemia with myeloblast proliferation, as well.5,6,7
Clinical signs
Clinical signs of erythremic myelosis are generally similar to other diseases causing severe anemia and result from insufficient oxygen delivery to tissues. These signs may include weakness and lethargy, depression, pale mucous membranes, increased respiratory rate and/or heart rate, and a systolic heart murmur.2,7 In addition, neoplastic cells may infiltrate and proliferate in various tissues and organs (Figure 3), promoting critical organ failure.
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| Figure 3. Fine-needle aspirate from the spleen of a cat with erythremic myelosis. The neoplastic infiltrate contains abundant erythroid precursors including numerous rubriblasts. A mitotic figure also is present (arrow). Wright-Leishman stain |
Clinicopathologic findings
Hematology - Severe anemia is a consistent finding with erythremic myelosis and the hematocrit may be as low as 4%.2,7,8 Other hematologic changes may include increased nucleated red blood cells with moderate to marked anisocytosis of erythrocytes and morphologic abnormalities consisting of macrocytosis, double nuclei, and asynchrony of nuclear and cytoplasmic maturation (Figure 4).2,3,5,8 Reticulocytes, as identified with new methylene blue staining (or polychromatophils, as identified with Romanowsky-type stains), are generally in the low-normal range or absent in the stained blood smears.2,3,8 Total white blood cell counts and platelet counts are variable.8
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Figure 4. Metarubricytes and rubricytes in the blood of cat with erythremic myelosis. Note the asynchrony of nuclear and cytoplasmic maturation in two metarubricytes (arrows) with hemoglobinized cytoplasm and retained nuclei. |
Bone Marrow - Changes within the bone marrow include a hypercellular marrow with a markedly decreased myeloid:erythroid (M:E) ratio and maturation arrest of the erythroid series, generally at the metarubricyte stage of development.2 More than 50% of all nucleated cells in bone marrow aspirates are erythroid precursors,1,7 and a proportion of the abnormal blast cells should show Periodic acid-Schiff (PAS) positive staining.3 The presence of siderocytes in the marrow precludes the possibility of an iron deficiency in which PAS-positive material may also be found in erythroid precursor cells.3,8 According to the adapted FAB classification system, erythremic myelosis is considered an erythroleukemia with erythroid predominance (M6-Er) when greater than 30% of the nucleated cells in the marrow are rubriblasts. Observing <30% blasts in the bone marrow is more consistent with a ‘pre-leukemic’ myelodysplastic syndrome (MDS-Er).1,4,8 Dysplasia of the granulocytic and megakaryocytic cell lines is variable.8
Prognosis
The diagnosis of erythremic myelosis carries a poor prognosis and is generally fatal. Consequently, all other causes of secondary dysmyelopoiesis (inflammatory disease, other neoplasia, etc.) should be excluded before the diagnosis of erythremic myelosis is made. A complete blood count with analysis of erythroid and myeloid morphology and examination of bone marrow aspirates or biopsy should be performed to support the diagnosis of erythremic myelosis. Cats diagnosed with erythremic myelosis also should be tested for feline leukemia virus infection because of the positive correlation of the two conditions.
Treatment
| Note:
Treatment of animals should only be performed by a licensed veterinarian.
Veterinarians should consult the current literature and current pharmacological
formularies before initiating any treatment protocol. |
Currently, there is no cure for feline erythremic myelosis. Treatment in cats is directed towards supportive care and may require repeated blood transfusions to temporarily reverse the effects of anemia and increase oxygen delivery to tissues.2,4 Other myeloproliferative disorders in FeLV-infected cats have responded to treatment with immunomodulating agents such as interferon and staphylococcal protein A.2,6 Chemotherapeutic drugs have had limited success with prolonged short-term survival,4,9 but the long-term prognosis remains grave.
References
1. Jain NC, Blue JT, Grindem CB, et al. A report of the animal leukemia study group: Proposed criteria for classification of acute myeloid leukemia in dogs and cats. Vet Clin Pathol. 1991;20:63-81.
2. Morrison JA. Erythremic Myelosis. Compen Contin Edu Practg Vet. 2001;23:880-885.
3. Falconer GJ, Irving AC, Watson PR, et al. A case of erythremic myelosis in a cat. New Zealand Veterinary Journal. 1980;28:83-84.
4. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat, 6th ed. St. Louis, Elsevier Saunders Co., 2005, p.656.
5. Withrow SJ, MacEwan EG. Small Animal Clinical Oncology, 3rd ed. Philadelphia, WB Saunders Co., 2001, p.596.
6. Engelman RW, Tyler RD, Mosier DA, et al. Changing manifestations of a chronic feline haematopoietic proliferative disease during immunotherapy with staphylococcal protein A. J Comp Pathol. 1986;96:177-204.
7. Comazzi S, Paltreinieri S, Caniatti M, et al. Erythremic myelosis (AML6er) in a cat. J Fel Med Surg. 2000;2:213-215.
8. Perkins P. Hematologic Abnormalities Accompanying Leukemia. In: Feldman BF, Zinkl JG, Jain NC, eds. Schalm’s Veterinary Hematology, 5th ed. Philadelphia, PA: Lippincott, Williams, and Wilkins, 2000, pp.743-744.
9. Shimada T, Matsumoto Y, Okuda Y et al. Erythroleukemia in two cats naturally infected with feline leukemia virus in the same household. J Vet Med Sci. 1995;57:199-204.
Acknowledgements
The image "Red Cat" by Michael Jurogue Johnson is from his website. It is copyrighted and used with permission of the artist, |