Felipedia

Erythremic myelosis is a myeloproliferative bone marrow disorder characterized by the presence of severe non-regenerative anaemia 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 anaemia; 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 anaemia 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


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.

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 anaemia. Cats infected with feline leukemia virus (FeLV) are predisposed to develop erythremic myelosis and other myeloid and lymphoid neoplasms such as myelomonocytic leukaemia. 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.⁴Cats with erythremic myelosis also may undergo blast transformation to erythroleukemia with myeloblast proliferation, as well.^5,6,7

Clinical signs of erythremic myelosis are generally similar to other diseases causing severe anaemia 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.


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	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 haemoglobinized cytoplasm and retained nuclei.

Haematology - Severe anaemia 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

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

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.

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 anaemia 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.