Department of Pathological Anatomy Acute myeloid leukemia Prepared

Department of Pathological Anatomy Acute myeloid leukemia Prepared by: GM 14 -24 -2 Imangali Maira Sotsialova Aidana Checked by: Head of department of Pathological Anatomy Sapargaliyeva Aigul

PLAN • • • Introduction Pathogenesis Classification Types Conclusion

INTRODUCTION • Acute myeloid leukemia (AML), • also known as acute myelogenous leukemia or acute nonlymphocytic leukemia (ANLL), • is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.

Pathogenesis

• Modern classification schemes for AML recognize the characteristics and behavior of the leukemic cell (and the leukemia) may depend on the stage at which differentiation was halted.

Classification

M 0 -M 3 • This scheme takes into account the degree of maturation M 0 acute myeloblastic leukemia, minimally differentiated 5% M 1 acute myeloblastic leukemia, without maturation 15% M 2 acute myeloblastic leukemia, with granulocytic maturation t(8; 21)(q 22; q 22), t(6; 9) 25% M 3 promyelocytic, or acute promyelocytic leukemia (APL) t(15; 17) 10%

Minimally differentiated acute myeloblastic leukemia(M 0)

Acute myeloblastic leukemia without maturation(M 1)

[ACUTE MYELOGENOUS LEUKEMIA, M 1, BLOOD]. AML-M 1 is defined by presence of more than 90% myeloblasts in blood and/or bone marrow and lack of any recurring chromosomal abnormalities such as t(8; 21), t(15; 17), inv(16) or t(16; 16)(p 13; q 22). The distinction between AML-M 1 and AML-M 2 not otherwise specified can be arbitrary than real since it merely depends on the blast count. AML-M 1 is also known as AML without maturation. Most blasts are large and typical of myeloblasts with prominent nucleoli.

[ACUTE MYELOGENOUS LEUKEMIA, M 1, BLOOD]. The defining feature of a myeloblast is fine nuclear chromatin and scant to moderate amount of cytoplasm. Note that myeloblasts may not show any cytoplasmic granules or Auer rods as in this case. The correct identification rests upon immunophenotyping which shows expression of myelomonocytic antigens such as CD 13, CD 15, CD 33, CD 117, and myeloperoxidase. The blasts generally also express CD 34 and HLA-DR.

[ACUTE MYELOGENOUS LEUKEMIA, M 1, BLOOD]. Multiple myeloblasts are shown with one myeloblast containing several fine rods-like structures called Auer rods are only seen in acute leukemias of myeloid differentiation.

Acute Myeloid Leukemia with Maturation (AMLM 2)

Acute promyelocytic leukemia M 3

[AML-M 3]. Acute myelogenous leukemia, M 3 type, also known as acute promyelocytic. This case illustrates hypergranular morphology with most cells containing abundant large granules (arrows). Note the lack of more mature myeloid elements, such as metamyelocytes, bands, and segmented neutrophils. Also note the lack of erythroid elements. Although most cases show Auer rods, this particular case did not contain any Auer rods. The lack of Auer rods is a rare but well documented finding. This case had t(15; 17) in all 20 metaphase cells and was also positive for PML-RAR fusion transcript by FISH study.

[AML-M 3]. This photomicrograph shows another important morphologic feature of hypergranular type; specifically, not only intact cells with abundant granulation are identified (arrow) but many ruptured cells are also seen releasing their granules free onto the slide (four arrowheads). The leukemic cells appear to be more fragile than normal promyelocytes and break apart upon smearing on the slides. In the absence of Auer rods, presence of abundant free large granules helps in differentiating leukemic promyelocytes from normal promyelocytes.

AML-M 3. This image depicts another morphologic feature of acute promyelocytic leukemia, that is, polarity of cytoplasmic granulation. In many cells the granules tend to polarize toward one portion of the cytoplasm and the nucleus on the opposite side (arrows). In normal promyelocytes the granules are distributed rather evenly throughout the cytoplasm and polarization is not a distinct and obvious feature. When cytoplasmic granulation is heavy and polarized it is a good telltale morphologic sign of acute promyelocytic leukemia in the appropriate clinical context.

AML-M 3. Acute promyelocytic leukemia often shows cells having dumbbell shaped or convoluted nuclear lobes (arrows). This feature is more common with hypogranular/microgranular form than hypergranular type but a few cells can usually be found in the hypergranular type as well. Normal promyelocytes DO NOT have dumbbell shaped or convoluted nuclear lobes.

AML-M 3. Although most cells may show the hypergranular morphology (arrow), some cells can have a hypogranular/microgranular or typical blast morphology with fewer and finer granules and fine chromatin (curved arrows). When most cells show typical blast morphology, distinction from other acute myelogenous leukemia is difficult and the final diagnosis rests upon demonstration of the typical t(15; 17) or positive FISH result for PML-RAR

M 4 -M 7 • Lineage of the leukemic blasts: M 4 acute myelomonocytic leukemia inv(16)(p 13 q 22), del(16 q) 20% M 4 eo myelomonocytic together with bone marrow eosinophilia inv(16), t(16; 16) 5% M 5 acute monoblastic leukemia (M 5 a) or acute monocytic leukemia (M 5 b) del (11 q), t(9; 11), t(11; 19) 10% M 6 acute erythroid leukemias, including erythroleukemia (M 6 a) and very rare pure erythroid leukemia (M 6 b) 5% M 7 acute megakaryoblastic leukemia t(1; 22) 5%

Acute myelomonocytic leukemia involves an uncontrolled proliferation of myeloblasts and monoblasts • More than 20% of the non-erythroid cells are monoblasts. • Monoblasts (like their mature counterpart, monocytes) have convoluted nuclei (A).

Acute monocytic leukemia blast cells in the bone marrow and blood precursors are represented essentially by monocytes. Note the nuclear folds and the relatively large nucleoli typical of monoblasts at right.

Acute erythroid leukemia myeloproliferation is of erythroblastic precursors

Types M 6 b (Pure erythroid leukemia) 80% erythroid precursors ranging from proerythroblasts to late polychromatophilic erythroid precursors (arrows).

Acute megacaryoblastic leukemia majority of the blasts are megakaryoblastic How looks megacaryoblasts?

Diagnosis requires more than 20% Blasts in the marrow/ peripheral blood with more than 50% demonstrating megakaryocytic derivation by morphology 20% 50%

Megacaryoblasts are: • Medium or large shaped • Huge nuclei • Light basophilic cytoplasm AML-M 7, bone marrow section

Causes • GATA-1 is a protein that in humans is encoded by the GATA 1 gene • Risk group: Children with Down Syndrome

Difference AML CML Acute Chronic producing abnormal cells in the bone marrow produces too much myeloid cells that prevent the creation of good cells has no known stages. has three stages of development, namely the chronic phase, the accelerated phase and the blasts crisis is a fast moving cancer that can spread to the entire body in a few short weeks is a slow moving cancer from the start

Conclusion Classification is based on the type of cell from which the leukemia developed and its degree of maturity. This is done by examining the appearance of the malignant cells with light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities.

References • http: //www. pathpedia. com/education/eatlas/histo pathology/blood_cells/aml-m 1. aspx • http: //www. cancernetwork. com/oncologyjournal/managing-acute-myeloid-leukemia-elderly • https: //quizlet. com/17133006/hematology-myeloidlymphoid-leukemia-flash-cards/ • Textbook of Pathology © 2010, Harsh Mohan • http: //taml. uchicago. edu/background/understandingacute-myeloid-leukemia/