Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (334 page)

   The 2008 WHO classification will guide the description of AML variants in this section. AML is divided into six major groups:

  1.  AML with recurrent genetic abnormalities: these abnormalities impact prognosis. The most common ones are balanced abnormalities that create a fusion gene encoding a chimeric protein. Best examples: acute promyelocytic leukemia (APL); AML with inv(16)(p13.1q22); AML with t(8;21) (q22;q22).

  2.  AML with myelodysplasia-related changes comprises three subgroups: AML arising from previous MDS or MDS/MPN; AML with an MDSrelated cytogenetic abnormality; AML with multilineage dysplasia. This group has a poor prognosis.

  3.  Therapy-related myeloid neoplasms: the leukemia occurs as a late complication of cytotoxic chemotherapy or radiation therapy.

  4.  AML not otherwise specified: cases that do not fulfill criteria for the other groups. These cases of AML are classified basically by morphology, and follow closely the FAB
^†
classification, except for having eliminated acute promyelocytic leukemia (formerly M3).

  5.  Myeloid sarcoma: extramedullary myeloid tumor. It may precede or coincide with overt AML.

  6.  Myeloid proliferations related to Down syndrome (DS): DS individuals have a 50- to 150-fold increase in the incidence of AML in the first 5 years of life. In some cases, the leukemia is acute megakaryocytic. In addition, 10% of DS newborns have
a transient
episode of abnormal myelopoiesis expressed mainly as thrombocytopenia and marked leukocytosis.

   Who Should Be Suspected?

   AML is the most common acute leukemia in adults. It should be suspected during the 1st months of life (initiating events are in utero), in middle age, or in the elderly, in a patient who is acutely ill, and with nonspecific presenting signs and symptoms that reflect profound disturbances in hematopoiesis: fatigue, malaise, infections, ulcerations of mucous membranes, bleeding, diffuse bone tenderness, joint pain, and swelling.

   Other findings:

   Modest splenic enlargement is present in 50% of cases.

   Lymphadenopathy is not present. Isolated masses (myeloid sarcoma [chloroma]), which are collection of blasts in extramedullary sites, may precede systemic AML.

   Laboratory Findings

Morphologic, cytochemical or immunophenotypic, cytogenetic, and molecular studies, if available, should be performed in every case to maximize the precise diagnosis and prognosis classification.

   CBC

   Anemia, normochromic, normocytic, is universally present. Nucleated red cells may be identified on the peripheral blood smear (PBS).

   Thrombocytopenia is severe in most cases.

   WBC: Leukocytosis with neutropenia is present in more than half the cases; some patients may present with leukopenia, especially if AML follows MDS. Greater than 20% of white cells are blasts. There are few or no intermediate granulocytic cells (myelocytes, metamyelocytes, bands). Auer rods are present in certain subtypes with granulocytic differentiation and help to establish the diagnosis, especially by determining myelogenous rather than lymphoid etiology at the first inspection of the patient’s peripheral blood smear (PBS).