WBC ANDF THAUR MORPHOLOGY THE VARIATIONSABNORMALITIES IN LEUCOCYTES

INTERPRETATION OF THE VARIATIONS/ABNORMALITIES IN LEUCOCYTES

A. Quantitative Changes

Neutrophil leucocytosis :-This denotes an increase in the number of neutrophils and is also called neutrophilia. Neutrophilia is seen in acute infec. tions, toxic conditions, acute haemorrhage, postoperative conditions, malignancies, etc. In severe cases, it is associated with appearance of earlier stages of maturation of myeloid cells in the peripheral blood. This is called shift to the left. Prominent granulation is also seen and is called toxic change. 

Neutropenia :- It is the reduction in neutrophils and occurs in aplastic anaemia, treatment with certain drugs, and in certain conditions such as bacterial, viral and parasitic infections.

  

Eosinophilia:- Increased eosinophil count may be seen in allergic reactions, parasitic infestations,asthma, some skin disorders, Hodgkin's disease and some leukaemias.

Basophilia:- Increase in basophils is not very frequently seen. It may occur in chronic myeloid leukaemia, chronic haemolytic anaemia, after splenectomy and irradiation.

Lymphocytosis:- It is seen characteristically in certain acute infections such as infectious mononucleosis, pertusis (whooping cough), mumps, rubella (German measles). It also occurs in chronic infections like tuberculosis, brucellosis, infectious hepatitis and in fungal infections.

Lymphopenia:-It may result as an effect of treatment with some drugs, and is also seen in acquired immune deficiency syndrome (AIDS).

Monocytosis I:-ncrease in monocytes may occur in infectious mononucleosis, malaria and some viral infections.

B. Qualitative (or morphological)Changes:-Most alterations in leucocyte morphology can be classified into three categories:

1. Toxic or reactive changes These are generally associated with bacterial infection or a toxic reaction.

2. Anomalous changes Deviation from the normal (anomaly) or irregularity can be congenital or acquired.

3. Malignant changes In leukaemia, there is an abnormal, uncontrolled proliferation of one or more of the various haemopoietic cells. They progressively displace normal cellular elements.

The affected cells may show morphological variations.

1.Toxic or reactive changes in leucocytes ;-

Hypersegmentation of nucleus:- Neutrophils with five or more lobes in the nucleus are typically seen in anaemias due to vitamin B12 and folic acid deficiency (megaloblastic or pernicious anaemia). The neutrophils are larger than normal in size.

 Cytoplasmic vacuolation:- indicates toxic change and may be followed by phagocytosis. The granules in the cytoplasm may be reduced in number.

Note A specimen anticoagulated with EDTA may also show cytoplasmic vacuoles. Toxic granulation

Toxic granules:- appear as deeply basophilic blue-black granules in the cytoplasm of neutrophils. The granules are larger in size than the normal neutrophilic granules. The toxic granules may be seen in conditions such as acute bacterial infection, burns and drug poisoning.

 Dohle bodies:- are seen in the cytoplasm of neutrophils as small, oval, light blue staining areas. The cytoplasmic RNA from the earlier stages of development may not be completely removed and appears as Dohle bodies. They may be seen in conditions such as infections, administration of toxic drugs, burn cases and pregnancy.

Basket cells or smudge cells :-These are damaged white cells showing degenerating nuclei without any cytoplasm. A few basket cells may be seen in a normal smear. However, they may be seen in large numbers in some leukaemias.

Turk cells:- These cells are similar to plasmacytes, but stain more deeply. They are found to be associated with viral infections.

Reactive lymphocytes :-These lymphocytes are seen in viral infections, particularly in infectious mononucleosis. The alterations from the normal form are due to an immune response to a stimulus. The nucleus may become loose and delicate, and is called reticular nucleus; or it may show heavy clumps of chromatin. The cytoplasm increases in volume, and shows amoeboid characteristics.

Barr Bodies:- A Barr body is a knob-like extension of the nuclear chromatin observed in some neutrophils in normal females. It is considered to be a sex chromatin (inactivated X-chromosome).

Auer Bodies or Auer Rods:- are found only in the cytoplasm of myeloblasts or promyelocytes in acute myeloid leukaemia. They appear as rodshaped, slender bodies, staining reddish-purple. They are only seen in the cells of myeloid series and are never seen in the lymphoid cells. Their presence in a leucocyte precursor, therefore, excludes lymphocytic leukaemia.

 2.Anomalies in leucocytes :-

Pelger-Huet anomaly:- can be inherited or acquired. In this anomaly, the nuclei of the granulocytes fail to segment. The nucleus may be seen as a band form, ring form of two lobes joined by a short filament. The nuclear chromatin is quite densely clumped. This condition may not have any clinical significance.

May-Hegglin anomaly :-In this type of anomaly, the neutrophils show spindle shaped inclusion bodies which stain grey-blue with Romanowsky group of stains. This disorder is hereditary and the patients have no clinical symptoms.

Alder-Reilly anomaly:- This anomaly is expressed as heavy granulation in all granulocytes and sometimes also in monocytes and lymphocytes. The anomaly is inherited.

below hows some causes of toxic changes and anomalies in leucocytes.

3. Malignant or leukaemic changes--:- Leukaemia is a disease of unknown aetiology with predisposing factors such as heredity, chemicals, radiation and viruses. Leukaemia is characterised by uncontrolled and abnormal formation of cells of one or more of the blood cell series.

Leukaemia is classified on the basis of the clinical course as acute and chronic. Acute leukaemia has a sudden onset and the disease progresses rapidly. Death is either due to haemorrhage or infection. 

Chronic leukaemia has a gradual onset and the symptoms may not be obvious for a long time. The patient usually survives for a much longer time, from 3–30 years. The cause of death may be unrelated to the disease.

Morphological Classification of Leukaemia

Leukaemia can be diagnosed from haematological investigations such as the complete blood count (especially WBC, RBC and platelet counts), examination of the peripheral blood smear and examination of the bone marrow smear. Leukaemia can be classified according to the cell type involved :

1. Myeloid (or non lymphocytic)

2. Lymphocytic

3. Monocytic

4. Erythroid

5.Plasma cell.

Each of the above types can be acute or chronic.

1

Characteristics of myeloid leukaemia:-

(i) There is marked leucocytosis. The cell count may range between 20,000–100,000/ cu.mm (20 to 100 x 10°/L ) in acute myeloid leukaemia (AML); and as high as 800,000/cu.mm (800 x 10°/L) in chronic myeloid leukaemia (CML). Sometimes in AML, the total leucocyte count may fall below 2,000/cu.mm. This is known as aleukaemic leukaemia.

(ii) In AML, about 30-90 % blast cells may be seen in the peripheral blood smear. Generally, more than 60 % blast cells indicates AML. On the other hand, CML will show about 1-10 % blast cells in the peripheral blood and contains all granulocyte developmental stages including mature forms.

(iii) An increased percentage of basophils (3-20 %), and sometimes eosinophils may be observed in CML, whereas in AML it is difficult to find mature forms of granulocytes.

(iv) Severe anaemia is a characteristic feature of AML due to decreased production of red cells. The red blood cells are generally normocytic and normochromic. CML is associated with a moderate degree of anaemia with mild anisocytosis and poikilocytosis.

(v) Thrombocytopenia (low platelet count) is very characteristic of acute leukaemia while platelet count is generally within the normal limits in chronic leukaemia. Therefore, in AML, bleeding time is prolonged, and clot retraction is poor.

(vi) Bone marrow is hypercellular showing hyperplasia of the myeloid series. In AML, the majority are blast cells while in CML all stages of myeloid maturation are also present. In both cases, red cell series is suppressed. Megakaryocytes are suppressed in AML and are unaffected in CML.

Characteristics of Lymphocytic Leukaemia:-

(i) There is an increase in total white cell count usually to about 200,000 to 250,000/cu.mm. (200 x 10°/L to 250 x 109/L)

(ii) In acute lymphocytic leukaemia (ALL), a large number of lymphoblasts (70 to 90 %) can be seen, while in chronic lymphocytic leukaemia (CLL), the percentage may be about 10 %.

(iii) There is normocytic, normochromic anaemia in both ALL and CLL.

(iv) The platelet count is normal or slightly reduced in later stages.

(v) Bone marrow is hypercellular with increase in the cells of lymphoid series while other cell types are suppressed.

Note:- It is difficult to differentiate between a myeloblast and a lymphoblast on the basis of morphology. Therefore, cytochemical and histochemical staining techniques (e.g. leucocyte alkaline phosphatase activity, esterase activity, periodic-acid-schiff (PAS) reaction) are used to identify abnormal precursors in blood with more accuracy.

Table 4 shows cytochemical methods for differentiation between AML and ALL.

Monocytic leukaemia:-The monocytic leukae mia has characteristics similar to those of myeloid leukaemia except that the predominant cell type is the precursor of monocyte, the monoblast.

Acute erythroid leukaemia:-Increased production of red cell precursors leads to acute erythroid leukaemia. The cells are usually megaloblastic and appear in the peripheral blood, bone marrow and sometimes, in the tissues. Sooner or later, these appearances change into acute myeloid leukaemia.

Plasma cell leukaemia:- This is a very rare condition where plasma cells are present in large numbers in the peripheral blood.