Page 378 - Textbook of Pathology, 6th Edition

362 1. Anaemia: Generally macrocytic or dimorphic. ACUTE MYELOID LEUKAEMIA
2. TLC: Usually normal; cases of CMML may have high Definition and Pathophysiology
TLC but these cases in WHO classification of myeloid
neoplasms have been put in a separate group of myelo- Acute myeloid leukaemia (AML) is a heterogeneous disease
dysplastic/myeloproliferative diseases and not in MDS. characterised by infiltration of malignant myeloid cells into
3. DLC: Neutrophils are hyposegmented and hypo- the blood, bone marrow and other tissues. AML is mainly a
granulated. Myeloblasts may be seen in PBF and their disease of adults (median age 50 years), while children and
number correlates with marrow blasts count. older individuals may also develop it.
AML develops due to inhibition of maturation of myeloid
4. Platelets: Thrombocytopenia with large agranular stem cells due to mutations. These mutations may be induced
platelets.
by several etiologic factors—heredity, radiation, chemical
BONE MARROW FINDINGS. There is constellation of carcinogens (tobacco smoking, rubber, plastic, paint,
findings in the marrow as under: insecticides etc) and long-term use of anti-cancer drugs but
1. Cellularity: Normal to hypercellular to hypocellular. viruses do not appear to have role in the etiology of AML.
2. Erythroid series: Dyserythropoiesis as seen by The defect induced by mutations causes accumulation of
abnormally appearing nuclei and ring sideroblasts. precursor myeloid cells of the stage at which the myeloid
Megaloblasts may be seen. maturation and differentiation is blocked. A few important
3. Myeloid series: Hypogranular and hyposegmented examples of chromosomal mutations in AML are
translocations {t(8;21)(q22q22) and t(15;17)(q22;q12)} and
SECTION II
myeloid precursor cells. Myeloblasts increased depending inversions { inv(16)(p13;q22)}.
upon the type of MDS.
4. Megakaryocyte series: Reduced in number and having Classification
abnormal nuclei.
Currently, two main classification schemes for AML are
followed:
Treatment and Complications
FAB CLASSIFICATION. According to revised FAB
MDS is difficult to treat and may not respond to cytotoxic clasification system, a leukaemia is acute if the bone marrow
chemotherapy. Stem cell transplantation offers cure and consists of more than 30% blasts. Based on morphology and
longer survival. Survival rates vary depending upon the cytochemistry, FAB classification divides AML into 8
type of MDS: cases of refractory anaemia with or without subtypes (M0 to M7) (Table 14.5).
sideroblasts (RA and RARS) and 5q syndrome survive for WHO CLASSIFICATION (2002). WHO classification for
years, while cases of refractory anaemia with excess blasts AML differs from revised FAB classification in the following
(RAEB-1 and 2) have poor survival for a few months only. 2 ways:
Patients generally either succumb to infections or develop 1. It places limited reliance on cytochemistry for making
into acute myeloid leukaemia. the diagnosis of subtype of AML but instead takes into

  TABLE 14.5: Revised FAB Classification of Acute Myeloblastic Leukaemias.
FAB Class Percent Cases Morphology Cytochemistry
M0: Minimally 2 Blasts lack definite cytologic and cytochemical Myeloperoxidase –
Haematology and Lymphoreticular Tissues
differentiated AML features but have myeloid lineage antigens
M1: AML without 20 Myeloblasts predominate; few if any Myeloperoxidase +
maturation granules or Auer rods
M2: AML with 30 Myeloblasts with promyelocytes predominate; Myeloperoxidase +++
maturation Auer rods may be present
M3: Acute promyelocytic 5 Hypergranular promyelocytes; often with Myeloperoxidase +++
leukaemia multiple Auer rods per cell
M4: Acute myelomonocytic 30 Mature cells of both myeloid and monocytic series Myeloperoxidase ++
leukaemia (Naegeli type) in peripheral blood; myeloid cells resemble M2 Non-specific esterase +
M5: Acute monocytic 10 Two subtypes: M5a shows poorly-differentiated Non-specific esterase ++
leukaemia monoblasts, M5b shows differentiated
(Schilling type) promonocytes and monocytes
M6: Acute erythroleukaemia <5 Erythroblasts predominate (>50%); myeloblasts Erythroblasts:PAS +
(Di Guglielmo’s and promyelocytes also increased Myeloblasts:
syndrome) myeloperoxidase +
M7: Acute megakaryocytic <5 Pleomorphic undifferentiated blasts predominate; Platelet peroxidase +
leukaemia react with antiplatelet antibodies