Pathology Thread

Acute Myeloblastic Leukemia without maturation - FAB M1

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.

Chromosome Abnormalities: t(9;22) Philadelphia chromosome, 8+, -5, and -7.

**** 2SMD should be familiar with each of the major types: M0-M7. The underlined phrases indicate the most important material for 2SMD.****

Acute Myeloblastic Leukemia with maturation - FAB M2

M2 is the most common (20-40%) type of AML.

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.

Chromosome Abnormalities: t(8;21), 8+, -5, and -7.

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.

Acute Promyelocytic Leukemia (APL) - FAB M3

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.

Chromosome Abnormalities: The t(15;17) is unique to promyelocytic leukemia.

Treatment Options: Why is it critical to distinguish M3 from other myeloid leukemias?

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.

Acute Myelomonocytic Leukemia (AMML) - FAB M4

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:

1. High serum lysozyme (3x normal)
2. A peripheral monocytosis of > 5x¹⁰/L in an otherwise M2 marrow and increased lysozyme
3. A peripheral monocytosis of >5 x¹⁰/L in M2 marrow and >20% NSE + marrow blasts. 

Chromosome Abnormalities: t(4;11), t(9;11), 8+ and -7.

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.

Acute Monocytic Leukemia (AMoL) - FAB M5

Differentiatiation: Monocytic.

Two subtypes:

• M5a is the poorly differentiated form
• M5b is the well-differentiated form

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.

fewer granules

occasionally will see slight nuclear fold

few, large nucleoli

more granules

typically round nucleus

more nucleoli

Acute Monocytic Leukemia (AMoL) - FAB M5a

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.

Acute Monocytic Leukemia (AMoL) - FAB M5b

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.

Acute Erythroblastic Leukemia - FAB M6

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.

* 30% considered adequate by some

(Ann Int Med 103:614,1985)

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).

Immunophenotype: Positive for glycophorin A.

Chromosome Abnormalities: 8+, -5, del(5q), and -7.

Differential Diagnosis: Congenital dyserythropoietic anemia, myelodysplastic syndrome, sideroblastic anemia, and megaloblastic anemia.

Acute Megakaryocytic Leukemia (AMKL) - FAB M7

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.

Morphology:
	M7 blasts may have granular cytoplasm and shed 'platelets'.	M7 blasts often clump together.

Diagnosis: Determination of an M7 subtype is dependent on immunologic evidence or electron microscopic ultracytochemical identification of platelet peroxidase (PPO).

Immunophenotypic studies of M7 are positive for glycoproteins GP Ib andGP IIb/IIIa.

Factor VIII related protein is usually found in the megakaryoblast cytoplasm.

Chromosome Abnormalities: t(1;22), have been associated with M7 in infants.

Myeloid Leukemia with Minimal Differentiation - FAB M0

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%).

Electron microscopic ultracytochemical studies for platelet peroxidase are negative.

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.

Chromosome Abnormalities: No particular association. 

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.

Extramedullary myeloid cell tumor (EMCT) or granulocytic sarcoma or chloroma is an extramedullary tissue mass of blasts and immature myeloid cells. The surface of a freshly cut EMCT turns light green (hence the name chloroma) upon exposure to air as large amounts of peroxidase are oxidized. EMCT may represent the initial manifestation of acute leukemia or signal relapse. The blast crisis of chronic myeloid leukemia may present as EMCT. Masses of monoblasts as may be seen in M5 leukemias are also sometimes referred to as EMCT.

The surface of this subcutaneous chloroma turned pale green after exposure to air. The patient had been in remission following Rx for AML.

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).

Abnormalities of chromosomes 5, 7, and 11 are common in therapy-induced leukemias.

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.