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t(1;14)(p32;q11.2) t(1;7)(q32;q35)

*These are example of chromosome abnormalities; the list is not intended to be comprehensive.

Figure 11.2 Acute myeloid leukemia with t(8;21) (q22;q22). Note Auer rod in myeloblast.

*These are example of chromosome abnormalities; the list is not intended to be comprehensive.

ence texts for an in-depth discussion of immunophe-notypes and genetics that are characteristic for each disorder.

Acute Myeloid Leukemia With t(8;21)(q22;q22)

This leukemia occurs most often in children or young adults and represents 5% to 12% of AML cases.25 The translocation t(8;21)(q22;q22) is the hallmark feature of this subtype. The morphology associated with this AML include the presence of myeloblasts having abundant cytoplasm, often containing azurophilic granules and sometimes containing large, pseudo-Chediak-Higashi granules. Auer rods are common, and maturation in the neutrophil lineage (promyelocytes, myelocytes, neu-trophils) is seen. Dysplastic neutrophilic features that may be seen include pseudo-Pelger-Huet hyposegmen-tation and hypogranulation. Eosinophils are often increased, and monocyte percentages are usually decreased (Fig. 11.2).

AML with t(8;21) is associated with good response to chemotherapy and long-term survival rates.

Acute Myeloid Leukemia With inv(16) (p13q22) or t(16;16)(p13;q22)

This acute myeloid leukemia occurs in all ages but most often in younger patients. The inv(16)(p13q22) is found in approximately 10% to 12% of all AML cases.19 This leukemia was previously referred to using the FAB classification as acute myelomonocytic leukemia with eosinophilia (AMML Eo). Various stages of monocytic,

Figure 11.2 Acute myeloid leukemia with t(8;21) (q22;q22). Note Auer rod in myeloblast.

granulocytic, and eosinophilic maturation are present, as well as abnormal granulations in the immature eosinophils (Fig. 11.3). Rarely, cases of inv(16)(p13q22) lack the eosinophilia.26 The monoblasts and promonocytes will stain positive for nonspecific esterase (NSE) stain, and the myeloblasts and monoblasts show greater than 3% positivity.

AMML with inv16 and t(16;16) also show high complete remission rates.

Acute Promyelocytic Leukemia [AML With t(15;17)(q22;q12)]

Acute promyelocytic leukemia (APL) accounts for 5% to 8% of AML and can occur in any age but most often

Figure 11.3 Acute myeloid leukemia with inv(16) (p13q22). Numerous monoblasts, promonocytes, and monocytes are present. Also note few eosinophils that are often characteristically increased in AML with this cytogenetic abnormality.
Promyelocyte Bone Marrow
Figure 11.4 (A) and (B), Hypergranular acute promyelocyte leukemia, promyelocytes with prominent azurophilic granules. (C) Hypergranular APL with multiple Auer rods. (D) Microgranular APLv. These abnormal promyelocytes have lobulated nuclei and absent or fine azurophilic granules.

in middle-aged patients.27 Abnormal, hypergranular promyelocytes predominate in the bone marrow in APL with t(15;17)(q22;q12). Numerous Auer rods (fused azurophilic granules) are present in the myeloblasts and promyelocytes, and bundles of Auer rods ("faggot cells") may be seen (Fig. 11.4, C). The azurophilic granules from leukemic promyelocytes have procoagulant activity and predispose the patient to a bleeding diathesis as a result of DIC. The MPO reaction is strongly positive in the promyelocytes. In about 20% of APL cases, a variant type of APL referred to as microgranular APL is found. These cases are characterized by cells with convoluted or lobulated nuclei that mimic promono-cytes (Fig. 11.4D). These leukemic promyelocytes contain such small azurophilic granules that they are not visible by light microscopy. These cells may cause confusion with acute monocytic leukemia; however, the strong positive MPO reaction (weak in AMonoL) and the bundles of Auer rods are clear clues pointing to a diagnosis of microgranular APL. In addition, the WBC

is often markedly elevated in the microgranular variety of APL.

The prognosis in APL patients with t(15;17) (q22;q12), as with the other leukemias grouped in this category, is also very good.

Acute Myeloid Leukemia With 11q23

This 11q23 deletion/translocation cytogenetic abnormality is found in 5% to 6% of AML cases. It occurs in more often in children but can occur at any age. Monoblasts and promonocytes predominate in the bone marrow and peripheral blood. The monoblasts have abundant cytoplasm, often showing pseudopodia, and fine nuclear chromatin with one or more nuclei. Azurophilic granules are often seen in the monoblasts, and cytoplasmic vacuoles may be present in monoblasts and promonocytes (Fig. 11.5). The NSE reaction is strongly positive in the monoblasts and promonocytes, and the MPO reaction is often negative. The prognosis in AML with 11q23 abnormalities is intermediate.

170 Part III • White Cell Disorders

170 Part III • White Cell Disorders

Figure 11.5 Acute myeloid leukemia with 11q23. Note monoblastic leukemia features; monoblasts have abundant cytoplasm, often showing pseudopodia, and fine nuclear chromatin, with one or more nucleoli.

II. Acute Myeloid Leukemia With Myelodysplasia

AML with myelodysplasia is seen primarily in adults.28 The blast percentage in blood or bone marrow is 20% or greater, with abnormal characteristics, called dysplasia, observed in at least two cell lines. Some of the dysplastic features that can be observed in neutrophils are hypogranulation, hyposegmentation or pseudo-Pelgeroid neutrophils, and/or bizarre segmented nuclei. In the erythroid cell line, the dyserythropoiesis may present as nucleated red cells with nuclear fragments or multinucleated cells, megaloblastic features, cytoplas-mic vacuoles, or karyorrhexis. Ringed sideroblasts may also be seen. The platelet cell line may also be dysplastic, as micromegakaryocytes with one lobe instead of multiple lobes are often present. It is important to be able to recognize these dwarf megakaryocytes because they may be seen by a technologist performing a peripheral smear examination and can be confused with other cells having a round nucleus, for example, mimicking the appearance of a myelocyte. The dysplasia must be present in at least two cell lines to fit the criteria for this category of AML. AML with myelodysplasia may follow a myelodys-plastic syndrome (see Chapter 14). Patients with this disorder often present with a decrease in WBC, RBC, and platelet counts, termed pancytopenia. The prognosis of patients with AML with myelodysplasia is poor.29

III. Therapy-Related Acute Myeloid Leukemia and Myelodysplastic Syndrome

Treatment with cytotoxic chemotherapy and/or radiation therapy has been associated with the development of AML and myelodysplastic syndrome. The two major agents implicated are alkylating agents/radiation and topoisomerase II inhibitors.30 These therapy-related leukemias have different epidemiologies, as the alkylating agent/radiation induced disorders usually occur 5 to 6 years after exposure, whereas the topoisomerase II inhibitor disorders occur after an average of 2 to 3 years after exposure.31 The alkylating agent-related AMLs usually start with a myelodysplastic presentation, with the blast percentage less than 5%, and having the typical myelodysplastic features. Nuclear hypolobulation, cytoplasmic hypogranulation, dyserythropoiesis, and an increase in ringed sideroblasts are characteristic features seen. This may progress into an AML or more pronounced myelodysplastic syndrome. There is a generally poor prognosis associated with alkylating agent/radiation therapy-related AML.

Topoisomerase II inhibitor-related AML does not usually have a preleukemic or myelodysplastic syndrome phase. This type of therapy-related AML often has morphology consistent with that seen in acute monoblastic or myelomonocytic leukemia, although cases showing involvement of other cell lineages have also been described. The prognosis is similar to that of patients with the corresponding morphologically classified AML.

IV. Acute Myeloid Leukemia (Not Otherwise Categorized)

Leukemias with features that do not fit into the previously described categories fall into this grouping. These leukemias are primarily classified according to morphology and cytochemistry reactions. As with the other AMLs, the presence of at least 20% blasts is a hallmark characteristic.

Acute Myeloid Leukemia, Minimally Differentiated

There is little evidence of maturation beyond the blast stage in AML, minimally differentiated, and the marrow is replaced by a homogeneous population of blasts (Fig. 11.6). The myeloid lineage of the blasts is defined by immunophenotyping with a positive expression of CD13, CD33, CD34, and CD117. The MPO and SBB cytochemical stains are usually negative (<3% blasts reacting) and Auer rods are absent. This phenotype comprises approximately 5% of the AML cases and is associated with a poor prognosis.

Acute Myeloid Leukemia Without Maturation

Similar to AML, minimally differentiated, the category of AML without maturation also involves cases where at least 90% of the nonerythroid cells in the bone marrow are myeloblasts (Fig. 11.7). However, at least 5% of the

Aml Minimal Differentiation
Figure 11.6 Acute myeloid leukemia, minimally differentiated.

Figure 11.8 Acute myeloid leukemia, with maturation. Note myeloblast with multiple Auer rods.

blasts, and usually a much higher percentage, have a positive reaction with MPO or SBB and Auer rods may be present. AML without maturation constitutes about 10% of AML cases. The blasts in this AML variant express CD13, CD33, CD34, and CD117. AML without maturation appears to have a poor prognosis, especially in patients with a markedly increased WBC.19

Acute Myeloid Leukemia With Maturation

AML with maturation is a common leukemia, comprising approximately 30% to 45% of all AML cases. Again, following the definition for acute leukemia, blasts will constitute at least 20% of all nucleated cells in the bone marrow. However, in this variant, greater than 10% of neutrophils with maturation beyond the promyelocyte stage are observed. Additionally, the monocytic component will comprise less than 20% of nonerythroid cells.

Aml Without Maturation
Figure 11.7 Acute myeloid leukemia, without maturation.

Blasts frequently demonstrate Auer rods and variable degrees of dysplasia may be seen (Fig. 11.8). More than 50% of the blasts and maturing cells are MPO and SBB positive. The morphology of the previously described AML with t(8;21)(q22;q22) is usually that of AML with maturation. This phenotype responds variably to chemotherapy, with the t(8;21) cases having a favorable prognosis.

Acute Myelomonocytic Leukemia

A mixture of malignant cells with both myelocytic and monocytic features are found in the blood and bone marrow of patients with acute myelomonocytic leukemia (AMML). The bone marrow has greater than 20% blasts, with both myeloid cells and monocytic cells each comprising greater than 20% of all marrow cells. The monoblasts are large cells with abundant, basophilic cytoplasm with fine azurophilic granules and often pseudopod cytoplasmic extensions; the nucleus has a lacy chromatin and one to four nucleoli. Promonocytes have a more convoluted nucleus with a somewhat more condensed, mature chromatin pattern and may have cytoplasmic vacuoles (Fig. 11.9). Interestingly, the monocytic component may be more prominent in the peripheral blood than in the bone marrow. The NSE reaction is usually strongly positive in AMML, and at least 3% of the blasts are MPO positive. The naphthol ASD chloracetate esterase (specific esterase) reaction is also positive. The leukemic cells variably express myeloid antigens of CD13 and CD33 and usually demonstrate one or more of the monocytic-associated antigens such as CD14, CD4, CD11c, CD64, and CD36.19 Cases of AML with inv(16) that display AMML with eosinophilia are discussed under AML with recurrent genetic abnormalities. This particular variant

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