Leukemia acute
General
Acute myeloid leukemia (AML) - general


Topic Completed: 1 December 2011

Revised: 7 February 2020

Copyright: 2001-2020, PathologyOutlines.com, Inc.

PubMed Search: Acute myeloid leukemia AML [title] pathology

Syed Zaidi, M.D.
Page views in 2019: 9,784
Page views in 2020 to date: 2,751
Cite this page: Zaidi S. Acute myeloid leukemia (AML) - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaAMLgeneral.html. Accessed March 29th, 2020.
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
FLT3 mutations
Definition / general:
  • Not a WHO diagnosis
  • Mutations of FMS related tyrosine kinase 3 (FLT3, gene located on 13q12) occur in all types of AML and MDS (Atlas of Genetics and Cytogenetics: FLT3 [Accessed 29 March 2018])
  • Most frequent molecular abnormality in AML (20 - 40% of cases)
  • AML: mutations occur most often in t(6;9)(p23;q34), APL t(15;17), AML with normal karyotype
  • Usually peripheral leukocytosis and normal cytogenetics
  • CD135 is receptor for FLT3 ligand / FLT3L

Prognostic factors:
  • Mutations include internal tandem duplication within juxtamembrane domain (ITD, 75 - 80%) and tyrosine kinase domain (TKD) in codon 836 (20 - 35%)
  • FLT3-ITD: poor prognosis (Blood 2002;100:1532)
  • FLT3-ITD with NPM1, t(15;17), t(8;21), inv(16) and t(16;16): worse prognosis
  • FLT3-ITD with CEBPA: unclear prognosis
  • FLT3-TKD: doesn't affect prognosis (Blood 2008;111:2527)

Treatment:
Microscopic (histologic) description:
Molecular / cytogenetics description:
  • Usually normal cytogenetics
  • Most common mutation is internal tandem duplication mutation (ITD)
  • Cooperating mutations with NPM1, CEBPA and MLL-PTD
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

AFIP images
Missing Image

Two myeloblasts each have a single prominent Auer rod

Missing Image

Auer rod in neutrophil

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:
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
  • Postchemotherapy or postradiation therapy
Differential diagnosis
  • Reactive process: growth factor treatment causes increased blasts
  • Transient myeloproliferative disorder of newborns: resembles AML-M7, ALL, myelodysplastic syndrome
Back to top