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Atlas Of Acute Leukemia (ALL, AML)

Table of Figures
Acute Leukemia - Undifferentiated leukemia - bone marrow

Acute Leukemia - Myeloblastic leukemia - bone marrow

Acute Leukemia - Other leukemias - bone marrow

Figures 13, 14

Figures 15, 16, 17

Figures 18, 19, 20

Acute erythroleukemia

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Acute leukemia is a disease of the leukocytes and their precursors. It is characterized by the appearance of immature, abnormal cells in the bone marrow and peripheral blood and frequently in the liver, spleen, lymph nodes, and other parenchymatous organs. The clinical picture is marked by the effects of anemia, which is usually severe (fatigue, malaise), an absence of functioning granulocytes (proneness to infection and inflammation), and thrombocytopenia (hemorrhagic diathesis). The spleen and liver usually are moderately enlarged, while enlarged lymph nodes are seen mainly in the pediatric lymphoblastic leukemias. Fever and a very high ESR complete the picture. Leukocyte counts vary greatly in the acute leukemias. About one-fourth to one-third of cases begin with a low white blood count (sub- or aleukemic leukemia), while about half show some degree of leukocytosis. Mature granulocytes may still be found in the peripheral blood in addition to abnormal forms. The coexistence of immature and mature cell forms is termed "hiatus leucaemicus." The leukocytopenic forms are the most difficult to differentiate from aplastic anemias, pancytopenias, and the myelodysplastic syndromes. Bone marrow aspiration is usually necessary to establish a diagnosis. Aspirated marrow is found to be permeated by abnormal cells (paramyeloblasts, paraleukoblasts, nonclassifiable cells (N. C. ), leukemic cells, blasts, etc.) with little or no evidence of normal hematopoiesis.

Classication of acute leukemias
Fig. 1. Classication of acute leukemias according to morphologic criteria. [From Begemann, H., Rastetter, J. eds. (1986) Clinical Hematology, 3rd ed., Thieme, Stuttgart.


The acute leukemias are classified according to morphologic, cytochemical, and immunologic criteria (Table 1). The FAB (French-American-British) classification system has become very widely adopted (Benett et al.1976). Besides cytochemical methods (Table 2), immunologic procedures have proved very useful for classifying the acute leukemias and especially for the differentiation of ALL and its subgroups.

Acute leukemia is closely related to erythroleukemia, a condition intermediate between acute erythremia and acute leukemia erythremia <— erythroleukemia —> myeloblastic leukemia.

Its clinical manifestations and course are basically identical to those of acute leukemia. Besides abnormal granulocytopoietic cells, the peripheral blood (Fig. 23d) contains numerous erythroid precursors which show conspicuous morphologic anomalies (megaloblastic and megaloblastoid cell forms) and are called "paraerythroblasts." These changes are even more impressive in the bone marrow (Figs. 21-23) where numerous karyorrhectic figures and abnormal mitoses are seen in the hyperplastic erythropoiesis. Differentiation from pernicious anemia can be problematic, although the erythroblasts of erythroleukemia are distinguished cytochemically by their high PAS activity (Fig. 23c).


Table 1. Classification of acute leukemias (modified from Pfreundschuh M. Hunstein W (1981) Krankenhausarzt 42:206)
Designation Morphology Occurrence Cytochemistry Immunology Biochemistry
FAB Tradition Cells Nucleus Nucleoli Cytoplasm Granules
Peroxidase-
Sudan black
NASDA NASDA
NaF-Inh.
PAS
L1 Acute lympboblastic
leukemia ALL
Small, uniform Round,
homogeneous
Not visible Scanty,
moderately basophilic
- 75% of childhood ALL - +/- +/- +++ 70% c-ALL
20% T-ALL
rarely B-ALL or null-ALL
TdT positive
L2 ALL Of varying size Irregular,
nonhomogeneous
One or more Variable - 70% of adult ALL - +/- +/- +++ 50% c-ALL
30% T-ALL
TdT positive
L3 Burkitt-type ALL Large, uniform Round-to-oval,
homogeneous
One or more,
vesicular,
often prominent
Abundant,
deeply basophilic
- Rare - +/- +/- +++ Usually B-ALL TdT positive
M1 Acute myeloblastic
leukemia without
signs of maturity
Large, regular Round, regular One or more Scanty - + + + -/+ Value of immunologic
differentiation with
monoclonal antibodies
remains unclear

M2 Acute myeloblastic
leukemia with
signs of maturity
Very large Kidney-shaped One or more Variable Numerous, scattered
Auer rods
M1+M2+M3
=45% of adult ANLL
+++ ++ ++ +
M3 Acute promyleocytic
leukemia
Very large Kidney Shaped One or more Variable Large numbers
of Auer rods (--DICIII)
+++ ++ ++ +
M4 Acute myelomonocytic
leukemia
Like M2+M5, each equaling
at least 20% in the marrow
or peripheral blood
=== === === === 40% of adult ANLL ++ +++ ++/+ ++/+ Lysozyme
(serum, urine)
M5 Acute monocytic
leukemia
large,
often lobulated
Indented Few visible Lightly basophilic Fine azure
granules
7% of adult ANLL +/- +++ +/- ++/+ Lysozyme
(serum, urine)
M6 Acute ertyhroleukemia Large, bizarre,
round-to-oval
Large, lobulated
round-to-oval
Multiple Often vacuolated,
variable
Rare - +/- +/- +++
-- Acute undifferentiated
leukemia
Often resembling
L1, L2,M1
Rare - - - -

Extremely rare forms of acute leukemia include acute eosinophilic leukemia, acute basophilic leukemia, and acute megakaryoblastic leukemia.

Table 2. Classification of acute leukemias by morphologic and cytochemical criteria (modified from Löffler)
Stem cell leukemia <=============> Lymphoblastic leukemia (ALL)
peroxidase 0 undifferentiated type preoxidase 0 periodic acid Schiff type
periodic acid Schiff 0 periodic acid Schiff +
alpha-napthylacetate esterase 0 alpha-naphthylacetate esterase 0
Myeloblastic leukemia (AML)
peroxidase (-) Peroxidase type 1 and 2
periodic acid Schiff 0-(+)
alpha-napthylacetate esterase (+)
Promyelocytic leukemia
peroxidase + Peroxidase type 3
periodic acid Schiff (+)
alpha-napthylacetate esterase (+)
Myelomonocytic leukemia
peroxidase + Peroxidase esterase type
periodic acid Schiff (+)
alpha-napthylacetate esterase +
Monocytic leukemia
peroxidase (+) Esterase type
periodic acid Schiff 0-(+)
alpha-napthylacetate esterase +
0 = negative; (+) = weakly positive < 25%; + = strongly positive > 50

Acute eosinophilic leukemia is diagnosed by examination of the bone marrow, since eosinophils usually are not increased in the peripheral blood. The predominant marrow cells are abnormal eosinophils (immature, pleomorphic forms, some with coarse, dark-blue granules, cytoplasmic vacuoles, distinct nucleoli). Diagnosis relies on the cytochemical detection of naphthol-AS-D-chloracetate esterase in the granules. Auer rods are unusual.

Acute basophilic leukemia is evidenced by an extreme increase in the basophilic granulated cells of granulocytopoiesis. The granules are very atypical (large, coarse, hyperchromic), and Auer rods may be present The diagnosis is confirmed by the metachromatic reaction to toluidine blue in the cells.

Four forms are recognized (after Quattrin 1978):

  1. basophilic blast crises in CML
  2. promyelocytic basophilic type
  3. histiobasophilic type
  4. basophilic-eosinophilic type

It is very difficult to establish a diagnosis of acute megakaryoblastic leukemia, designated M7 in the FAB classification of acute leukemias (Benett et al. 1985). The blast cells in the peripheral blood and bone marrow present a variety of morphologies. They may appear as small cells with a narrow cytoplasmic border and dense chromatin, resembling lymphoblasts (L1), or they may resemble L2 cells with or without granules. The nuclei are round, finely reticular, and have one to three prominent nucleoli. The cells vary greatly in size and may be two to three times larger than normal lymphocytes. Sometimes one finds cytoplasmic vesicles or differentiated megakaryocytes with adjacent platelets or bare nuclei nested in clusters of platelets. Occasional megakaryocytic nuclei are found in the peripheral blood. It is often difficult to obtain a bone marrow specimen by aspiration, and marrow biopsy is usually indicated. Cytochemical methods may contribute to the diagnosis. The Sudan black and peroxidase reaction are negative. The monocytes can be a source of confusion. Often they are positive for alpha-napthylesterase and naphthyl-ASD-acetate esterase, in which case these enzymes canbe inhibited by fluoride. While the monocytes usually show a diffuse positivity for these esterase enzymes, the reaction in megakaryoblasts tends to be localized. PAS and acid phosphatase positivity are also localized. A platelet peroxidase occuring on a nuclear membrane and in the endoplasmic reticulum of megakaryoblasts can distinquish these cells from myeloblasts on electron microscope examination. This can also be accomplished by the use of monoclonal or polyclonal platelet-specific antibodies.

Figures 2 through 23 illustrate the great morphological diversity of the acute leukemias.



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