Escolar Documentos
Profissional Documentos
Cultura Documentos
cfm
PATHOLOGY
Pathology > Basic Hematology > White Cell Disorders > Leukemia: Acute Non-Lymphoid Leukemia
Minimal maturation ( > 90% type I and II blasts ) of marrow nonerythroid cells is present. Most of the blasts are agranular. Auer
rods are infrequent.
Staining: Relatively few blasts (5-10%) are MPO (myeloperoxidase) positive. A minimum of 3% MPO positive blasts are required
for diagnosis. NSE and PAS are generally negative.
Immunophenotype: Variably positive for CD13, CD14, CD11b, CD33, and HLA-DR.
**** 2SMD should be familiar with each of the major types: M0-M7. The underlined phrases indicate the most important material
for 2SMD.****
Maturation: Type II blasts are common and Auer rods are frequent (promyelocytes-myelocytes).
Staining: The blasts are largely MPO positive. NSE and PAS are generally negative.
Immunophenotype: Variable positivity for CD13, CD33, and HLA-DR, but are negative for CD14
and CD11b.
Cell Morphology: In some cases the immature cells have abundant, frequently basophilic
cytoplasm, with variable numbers of often indistinct, sometimes coalescent granules. If such
immature cells are < 10% the diagnosis is M1, but if > 10% the diagnosis becomes M2.
Maturation: In the classic M3 the majority of the proliferating cells are abnormal promyelocytes with
numerous primary type granules. Auer rods are frequent and often multiple.
Staining: The cells are MPO and chloroacetate esterase (CAE) positive, but generally negative for NSE
(NSE positive in 25%).
Immunophenotype: Positivity for CD13 and CD33, but are usually negative for HLA-DR.
1 of 5 15/05/2011 18:31
Pathology http://www.med-ed.virginia.edu/courses/path/innes/wcd/myeloid1.cfm
Microgranular Variant: In the microgranular variant, M3v, the leukemic cells have a monocytic appearance with clefted
angel-wing nuclei and abundant cytoplasm having at best indistinct cytoplasmic granulation.
The cytochemical, immunophenotypic and chromosomal features are indentical to the classic M3.
Both forms of acute promyelocytic leukemia are associated with a high incidence of disseminated intravascular
coagulation (DIC) and hemorrhage.
Maturation: Differentiation along both myeloid and monocytic lines. Monocytes and promonocytes
represent > 20%, but < 80% of the marrow differential.
Staining: More than 20% of the blasts should be MPO + and more than 20% should be NSE + .
Diagnosis Aides:
Variant: M4e variant in which eosinophils (> 5%) are increased in number and abnormal associated with
abnormalities of chromosome 16.
Staining of Variant: CAE, usually negative in eosinophils, is frequently positive in the abnormal
eosinophils of M4e.
Differentiatiation: Monocytic.
Two subtypes:
Chromosome Abnormalities: t(9;11), 8+, -5, and -7. Chromosome abnormalities of 11q are closely associated
with M5a
Cell Morphology: Note the nuclear folds and the relatively large nucleoli typical of monoblasts at right.
Monoblasts Myeloblasts
fewer granules more granules
2 of 5 15/05/2011 18:31
Pathology http://www.med-ed.virginia.edu/courses/path/innes/wcd/myeloid1.cfm
This is the M5a or poorly differentiated form of acute monoblastic leukemia. >80% of cells are monoblasts.
Staining: The blasts in M5a are generally MPO negative, but strongly positive for the nonspecific esterase (NSE) and inhibited by Fluoride.
This is the M5b or differentiated form of acute monoblastic leukemia in which > 80% of the leukemic cells are monoblasts, promonocytes, and monocytes. Note
the large nucleoli so typical of monoblasts
Staining: The blasts of M5b usually contain some peroxidase activity and, of course, are positive for nonspecific esterase (NSE) and inhibited by Fluoride.
Maturation: M6 or erythroleukemia is rare and difficult to diagnose. More than 50%* of the nucleated
marrow cells are abnormal nucleated red blood cells.
Morphology: The leukemic red cells are frequently bizarre with extreme dysplastic features including:
giant forms, multinucleation, cytoplasmic vacuolization, cytoplasmic buds, and megaloblastoid changes.
Staining: The blasts are MPO negative, but often positive for NSE. The malignant red cells are PAS positive, (forming PAS positive lakes or containing coarse
chunks of PAS positive material).
Differential Diagnosis: Congenital dyserythropoietic anemia, myelodysplastic syndrome, sideroblastic anemia, and megaloblastic anemia.
M7 blasts are often resemble lymphoblasts, although M7 leukemias may be accompanied by atypical megakaryocytes. The marrow is often fibrotic.
Staining: M7 blasts are MPO negative and variably positive for PAS and NSE.
3 of 5 15/05/2011 18:31
Pathology http://www.med-ed.virginia.edu/courses/path/innes/wcd/myeloid1.cfm
Morphology:
M0 is a recently defined FAB nonlymphoid leukemia dependent on the immunologici dentification of myeloid antigens.
Morphologic and cytochemical studies show nodistinguishing features.
Staining: M0 blasts are nondescript (no Auer rods) and are MPO, PAS and NSE negative (<3%).
Immunophenotype: M0 blasts are negative for B and T lymphoid antigens, platelet glycoproteins GP Ib and GP
IIb/IIIa, and erythroid glycophorin A. Myeloid antigens such as CD13, CD33 and CD11b are variably positive. CD34 and
HLA-DR are generally positive.
Eosinophilic leukemia is a rare variant of acute myeloid leukemia in which blasts and immature eosinophils
proliferate. CNS involvement appears to be common. Should be distinguished from CML with large numbers of
eosinophils.
Basophilic leukemia is a rare subset of AML associated with t(6;9) and abnormal 12p. Ultrastructural studies of the
immature basophilic granules may be necessary. Philadelphia chromosome positive cases may be related to the
blast crisis of CML.
The surface of this subcutaneous chloroma turned pale green after exposure to air. The patient had
been in remission following Rx for AML.
4 of 5 15/05/2011 18:31
Pathology http://www.med-ed.virginia.edu/courses/path/innes/wcd/myeloid1.cfm
Granulocytic sarcoma may represent the initial manifestation of acute leukemia or signal relapse.
Acute myeloid leukemia may present as gum infiltrates, especially in cases of acute myelomonocytic
leukemia (FAB M4) and monoblastic leukemia (FAB M5).
Blast crisis of chronic leukemia refers to a phase of a chronic leukemia resembling an acute leukemia ( in which blasts are >30%). In chronic myelogenous
leukemia (CML), blast crisis signals the terminal phase of the disease for which there is no effective therapy.
Secondary (therapy-induced) acute leukemia is nearly always myeloid and is usually preceeded by a myelodysplastic syndrome involving all three hematopoietic
cell lines (panmyeloisis).
This is most common after alkylating chemotherapy or radiation therapy, with an average latent period of 5 years (range1-15 years).
Hypocellular acute leukemia is a situation in which the marrow cellularity (< 30%) often resembles aplastic anemia, but with numerous (>30%) blasts in the
interstitium of the marrow. About 5-10% of acute myeloid leukemias present in this form.
Department of Pathology
PO Box 800214
UVa Health System
Charlottesville, VA 22908
Tel:(434) 924-5198
5 of 5 15/05/2011 18:31