Part III • White Cell Disorders to 6% of AML cases. Characteristics that are commonly seen in the abundant erythroid precursors include dysplastic features such as bizarre multinucleation, cytoplasmic vacuolization, and megaloblastic nuclear changes. The differential diagnosis includes megaloblastic anemia; however, patients with vitamin B12 or folic acid deficiency will respond to treatment with these vitamins, and the dysplastic features are not as pronounced as those seen in cases of erythroleukemia.

Myeloblasts containing Auer rods may be observed in up to two-thirds of patients with erythroleukemia.34 Abnormal megakaryocytes may also be noted. Anemia is often markedly severe in patients with erythroleukemia, and indeed may be more profound that the degree seen in other AML subtypes. The peripheral blood may contain a striking amount of nucleated red cells. However, it is interesting to note that the crowding of the normal elements of the bone marrow by the leukemic cell population results in ineffective erythropoiesis, which actually leads to reticulocytopenia. The bone marrow iron stain often demonstrates ringed sideroblasts, and the PAS stain may be positive in the classic "block" or coarse pos-itivity in the pronormoblasts. The myeloblasts will stain MPO and SBB positive.

Pure erythroid leukemia is the more rare subtype of the two acute erythroid leukemias and may be seen in any age. The stem cells in this leukemia give rise predominantly to erythroid lineage; therefore, any myeloid cell markers will be negative. The pronormoblasts can be identified by immunohistochemical reactivity with antibody to hemoglobin A and expression of gly-cophorin A, a red cell membrane protein.19

Erythromyeloleukemia may evolve to an acute myeloblastic leukemia, with similar prognostic results as other subtypes in patients of similar ages.35 Pure ery-throid leukemia is usually associated with an aggressive clinical course.

Acute Megakaryoblastic Leukemia

Acute megakaryoblastic leukemia (AMegL) is the most rare form of the AMLs, comprising approximately 3% to 5% of cases. This diagnosis is made if at least 20% of blasts in the bone marrow are megakaryoblasts. This leukemia occurs in both children and adults.

Megakaryoblasts are small, medium to large in size, often found as heterogeneous mix in the same patient in regard to size, with some blasts being of small or medium size with scant basophilic cytoplasm and others much larger with more abundant cytoplasm and distinct blebbing pseudopod formation. The nucleus is round or slightly indented with delicate chromatin and one to three prominent nucleoli. Although megakary-

Figure 11.12 Acute megakaryoblastic leukemia.

oblasts may be difficult if not impossible to identify by light microscopy, the presence of blasts with cytoplas-mic blebbing may provide a hallmark clue as to the lineage of the blasts. Megakaryoblastic fragments or micromegakaryocytes, along with giant, hypogranular platelets, are sometimes present (Fig. 11.12).

The diagnosis of AMegL is usually made based on immunophenotyping results because megakaryoblasts will express one or more of the platelet glycoproteins: CD41 (glycoprotein Ilb/IIIa), CD61 (glycoprotein Ilia), and, less frequently, CD42 (glycoprotein Ib). Cyto-chemical stains are not as useful, as the MPO, SBB, and TdT are negative, whereas the alpha-naphthyl acetate esterase reaction is usually positive with a negative alpha-naphthyl butyrate esterase reaction (both types of NSE would be positive in acute monocytic leukemia). Megakaryoblasts manifest platelet peroxidase activity that can be identified by electron microscopy cytochemistry.

Although adult patients usually present with the typical acute leukemia symptoms related to cytopenias of pallor, weakness, and excessive bleeding, unlike other leukemias, organomegaly is uncommon at diagnosis. Thrombocytosis may rarely occur and dysplastic features of platelets and neutrophils may be seen. The AMegL that occurs in children has been associated with t(1;22), and these individuals may present with significant abdominal masses36 and lytic bone lesions.37 Children with Down syndrome who develop an acute transient leukemia often have AMegL as the predominant morphological subtype. Patients with this rare form of AMegL associated with Down syndrome may undergo spontaneous remission, in contrast with the poor prognosis that is typical of most cases of AMegL, especially in infants with the t(1:22).38

Other Acute Leukemias

Several other acute leukemias account for less than 5% of cases of acute leukemia. Acute basophilic leukemia is a very rare leukemia that may occur "de novo" or more commonly may arise as a blastic transformation in patients with a preceding CML. The predominant circulating cell appears blast-like with one to three nucleoli and prominent, but variable number of, coarse basophilic granules. The cells will stain positive with the metachromatic stain tolidine blue. Additionally, the blasts will stain positive with acid phosphatase and show block positivity with PAS but are negative with MPO, SBB, and NSE stains. The blasts usually are positive for myeloid markers CD13, CD33, and CD34, and also will show reactivity with CD9. The special stains and immunophenotyping will distinguish acute basophilic leukemia from acute promyelocytic leukemia, as the early basophilic myelocytes may be confused with promyelocytes.

Acute myelofibrosis is another rare leukemia characterized by marked peripheral blood pancytopenia and marrow hyperplasia of the erythroid, granulocytic, and megakaryocytic components, combined with a variable degree of fibrosis. Differential diagnosis from chronic idiopathic myelofibrosis (IMF) can be made since more immature cells are seen in the acute process and the splenomegaly that is a hallmark feature of IMF is absent in acute myelofibrosis.

There are several types of acute leukemias that the WHO group has combined into "acute leukemia of ambiguous lineage." These include leukemias where the morphologic, immunophenotypic, and/or cyto-chemical findings are not helpful in the classification of a particular type of myeloid or lymphoid process or, conversely, where the features indicate a combination of different lines.39-41 Undifferentiated acute leukemias lack markers consistent with a specific lineage, bilineal acute leukemias contain different populations of cells that express both myeloid and lymphoid markers, and biphenotypic acute leukemias are typified by cells that have both myeloid- and T or B lineage-specific antigens on the same blast population.19

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