Leukemia - Acute
General
Acute myeloid leukemia (AML) - general

Author: Syed Zaidi, M.D. (see Authors page)

Revised: 27 March 2018, last major update December 2011

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: Acute myeloid leukemia AML [title] pathology

Cite this page: Zaidi, S. AML general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaAMLgeneral.html. Accessed October 17th, 2018.
Definition / general
  • Also called acute myelogenous leukemia
  • Clonal neoplastic proliferation of hematopoietic precursor cells causing excessive myeloblasts and other immature myeloid cells
Clinical features
  • Malignant cells replace bone marrow, may infiltrate spleen, liver and lymph nodes and circulate in bloodstream
  • Usually less nodal involvement than ALL
  • 80% of adult leukemias but only 20% of childhood leukemias
  • Neoplastic blasts have normal proliferation rates but reduced maturation rates compared to normal blasts

Risk factors:
  • Most patients have none
  • Drugs (alkylating agents, Topoisomerase II inhibition, antimetabolites, antitubulin agents), radiation therapy
  • Down syndrome
  • Bloom syndrome
  • Fanconi anemia
  • Neurofibromatosis
  • Benzene exposure

Symptoms:
  • Due to replacement of normal bone marrow cells by blasts
  • Fatigue (due to anemia)
  • Fever and opportunistic infections (due to neutropenia)
  • Mucosal and cutaneous bleeding (due to thrombocytopenia)
  • Tissue infiltration with myelomonocytic, monocytic and monoblastic leukemia, including gingival hyperplasia and leukemia cutis (monocytes tend to infiltrate)
  • Sternal tenderness (due to bone marrow expansion)
  • Neurological symptoms (due to CNS infiltration)

Laboratory:
  • 50% have WBC > 10,000, 20% have WBC > 100,000
  • Due to circulating blasts and other immature myeloid cells
  • In aleukemic leukemia, peripheral blood lacks blasts, and must examine bone marrow

Diagnosis:
  • Examination of blood, marrow smears and cytochemical stains is usually sufficient
  • Immunostains may be required for poorly differentiated leukemia
Prognostic factors
Favorable Prognostic Factors:
  • Young patients
  • Rapid response to chemotherapy
  • Favorable cytogenetics - see below

Unfavorable Prognostic Factors:
Treatment
  • Chemotherapy cures 10 - 30% (induction, consolidation, maintenance phases)
  • Allogeneic bone marrow transplantation cures 45 - 65%
  • 5 year survival only 20% in adults, 50% in children (Oncologist 2007;12:341)
Microscopic (histologic) description
Peripheral smear:
  • Anisopoikilocytosis (variation in size and shape of red blood cells)
  • Nucleated red cells
  • Neutropenia
  • Thrombocytopenia
  • Hypogranular and hyposegmented neutrophils
  • Large atypical platelets

Aspirate micro smears:
  • Myeloblasts are usually larger than lymphoblasts of ALL
  • Cytoplasm is more abundant, with fine azurophilic granules and Auer rods (abnormal crystallized azurophilic granules, particularly in promyelocytic leukemia)
  • Delicate nuclear chromatin with 1 - 4 prominent nucleoli
  • Often dysplastic, maturing myeloid cells

Micro biopsy:
  • Usually markedly hypercellular with immature appearing cells but no trilinear maturation
  • By definition, at least 20% blasts
  • Mitotic activity common
  • May have myelofibrosis(though uncommon)
  • See also descriptions of various AML subtypes
  • Type I myeloblasts: no cytoplasmic granules; nucleus is large with delicate chromatin and prominent nucleolus
  • Type II myeloblasts: 15 - 20 delicate cytoplasmic granules
  • Type III myeloblasts: > 15 - 20 cytoplasmic granules, but otherwise has features of a blast cell
  • Microscopic (histologic) images

    Images hosted on PathOut server:
    Missing Image

    Two myeloblasts each have a single prominent Auer rod

    Missing Image

    Auer rod in neutrophil

    Molecular / cytogenetics description
    • 90% have chromosomal abnormalities
    • De novo leukemia often has balanced translocations, but therapy related or post-myelodysplasia leukemia often has deletions or monosomy 5 or 7 without translocations

    Favorable Cytogenetics:
    • inv(16)(p13;q22), t(8;21)(q22;q22), t(15;17)(q22;q12)

    Intermediate Cytogenetics:
    • +8, t(6;9)(p23;q34), t(9;11)(p22;q23) in children
    • Normal cytogenetics

    Unfavorable Cytogenetics:
    • -7, -5, del 7q, t(11q23), inv(3q), t(9;22)
    • Complex abnormalities
    • Post-chemotherapy or post-radiation therapy
    Positive stains
    Positive enzyme cytochemistry
    • Myeloperoxidase (Mod Pathol 1991;4:733), Sudan Black B, chloroacetate esterase (stains lysosomes in granulocytes)
    • Variable for acid phosphatase
    • M4/M5 are positive for nonspecific esterase (alpha naphthyl butyrate esterase)
    • M5/M6/M7 are positive for PAS
    • Alpha-naphthyl acetate esterase (ANAE): also called modified nonspecific esterase; stains some T cells (Klin Lab Diagn 1993;6:38) and monocytic cells (Leuk Res 1998;22:25), but not erythroid cells
    • Alpha-naphthyl butyrate esterase: also called nonspecific esterase; stains monocytes and some T cells (J Exp Med 1981;153:182)
    • Chloroacetate esterase: also called specific esterase, naphthol AS-D chloroacetate esterase, Leder stain; stains granulocytes and mast cells, but not monocytes or lymphocytes
    Negative stains
    Flow cytometry description
    Immunohistochemmistry compared with flow cytometry:
    Differential diagnosis
    • Reactive process: growth factor treatment causes increased blasts
    • Transient myeloproliferative disorder of newborns: resembles AML-M7, ALL, myelodysplastic syndrome