Атлас по гематологии (английский язык)

Abnormalities of the White Cell Series

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

62 Abnormalities of the White Cell Series

A very old-fashioned, intuitive way of classifying CBCs is to divide them into those in which round to oval (mononuclear) cells predominate and those in which segmented (polynuclear) cells predominate. However, this old method does allow the relevant differential diagnosis to be inferred from a cursory screening of a slide.

Differential Diagnostic Notes

Differential diagnosis when round to oval cells predominate

Reactive lymphocytoses and monocytoses, pp. 67f., 89

Lymphatic system diseases (lymphomas, lymphocytic leukemia), p. 70

Acute leukemias, including episodes of chronic myeloid leukemia (CML), p. 96ff.

Low counts of cells with segmented nuclei (agranulocytosis– aplastic anemia–myelodysplasia), pp. 86, 106, 148

Differential diagnosis when segmented cells predominate

Reactive processes, p. 112ff.

Chronic myeloid leukemia, p. 114ff.

Osteomyelosclerosis, p. 122

Polycythemia vera, p. 162ff.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Predominance of Mononuclear Round

to Oval Cells (Table 5)

The cell counts (per microliter) show a wide range of values and depend on a variety of conditions even in normal blood. Any disease may therefore result in higher (leukocytosis) or lower cell counts (leukopenia). The assessment of cell counts requires the knowledge of normal values and their ranges (spreads) (Table 2, p. 12). The most important diagnostic indicator therefore is not the cell count but the cell type. In a first assessment, mononuclear (round to oval) and polynuclear (segmented) cells are compared. This is the first step in the differential diagnosis of the multifaceted spectrum of blood cells.

Absolute or relative predominance of mononuclear cells points to a defined set of diagnostic probabilities. The differential diagnostic notes opposite can help with a first orientation.

Consequently, the most important step is to distinguish between lymphatic cells and myeloid blasts. The nuclear morphology makes it possible to distinguish between the two cell types. In lymphatic cells the nucleus usually displays dense coarse chromatin with slate-like architecture and lighter zones between very dense ones. In contrast, the immature cells in myeloid leukemias contain nuclei with a more delicate reticular, sometimes sand-like chromatin structure with a finer, more irregular pattern.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

64 Abnormalities of the White Cell Series

Table 5 Diagnostic work-up for abnormalities in the white cell series with mononuclear cells predominating

Diagnostic steps proceed from left to right. | The next step is usually unnecessary; !optional step, may not progress the diagnosis; → the next step is obligatory.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

66 Abnormalities of the White Cell Series

Reactive Lymphocytosis

Lymphatic cells show wide variability and transform easily. This is usually seen as enlarged nuclei, a moderately loose, coarse chromatin structure, and a marked widening of the basophilic cytoplasmic layer.

Clinical findings, which include acute fever symptoms, enlarged lymph nodes, and sometimes exanthema, help to identify a lymphatic reactive state. Unlike the case in acute leukemias, erythrocyte and thrombocyte counts are not significantly reduced. Although the granulocyte count is relatively reduced, its absolute value (per microliter) rarely falls below the lower limit of normal values.

Morphologically normal lymphocytes predominate in the blood analyses in the following diseases:

Whooping cough (pertussis) with clear leukocytosis and total lymphocyte counts up to 20 000 and even 50 000/µl; occasionally, slightly plasmacytoid differentiation.

Infectious lymphocytosis, a pediatric infectious disease with fever of short duration. Lymphocyte counts may increase to "50 000/µl.

Chickenpox, measles, and brucellosis, in which a less well-developed relative lymphocytosis is found, and the counts remain within the normal range.

Hyperthyroidism and Addison disease, which show relative lymphocytosis.

Constitutional relative lymphocytosis, which can reach up to 60% and occurs without apparent reason (mostly in asthenic teenagers).

Absolute granulocytopenias with relative lymphocytosis (p. 86).

Chronic lymphocytic leukemia (CLL), which is always accompanied by absolute and relative lymphocytosis, usually with high cell counts.

Transformed, “stimulated” lymphocytes (“virocytes”) predominate in the CBC in the following diseases with reactive symptoms:

Lymphomatous toxoplasmosis does not usually involve significant leukocytosis. Slightly plasmacytoid cell forms are found.

In rubella infections the total leukocyte count is normal or low, and the lymphocytosis is only relatively developed. The cell morphology ranges from basophilic plasmacytoid cells to typical plasma cells.

In hepatitis the total leukocyte and lymphocyte counts are normal. However, the lymphocytes often clearly show plasmacytoid transformation.

The most extreme lymphocyte transformation is observed in mononucleosis (Epstein–Barr virus [EBV] or cytomegalovirus [CMV] infection) (p. 68).

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Extreme transformation of lymphocytes leads to blast-like cells: mononucleosis

a b

c d

Fig. 22 Lymphocytes during viral infection. a “Blastic,” lymphatic reactive form (Pfeiffer cell), in addition to less reactive virocytes in Epstein–Barr virus (EBV) infection. This phase with blastic cells lasts only a few days. b Virocyte (1) with homogeneous deep blue stained cytoplasm in EBV infection, in addition to normal lymphocyte (2) and monocyte (3). c Virus infection can also lead to elevated counts of large granulated lymphocytes (LGL) (1). Monocyte (2). d Severe lymphatic stress reaction with granulated lymphocytes. A lymphoma must be considered if this finding persists.

69

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.

70 Abnormalities of the White Cell Series

Diseases of the Lymphatic System

(Non-Hodgkin Lymphomas)

Malignant diseases of the lymphatic system are further classified as Hodgkin and non-Hodgkin lymphomas (NHL). NHL will be discussed here because most NHLs can be diagnosed on the blood analysis.

Non-Hodgkin lymphomas arise mostly from small or blastic B-cells.

Small-cell NHL cells are usually leukemic and relatively indolent, of the type of chronic lymphocytic leukemia and its variants.

Blastic NHL (precursor lymphoma) is not usually leukemic. An exception is the lymphoblastic lymphoma, which takes its course as an acute lymphocytic leukemia.

Plasmacytoma is an osteotropic B-cell lymphoma that releases not its cells but their products (immunoglobulins) into the bloodstream.

Malignant lymphogranulomatosis (Hodgkin disease) cannot be diagnosed on the basis of blood analysis. It is therefore discussed under lymph node cytology (p. 176).

The modern pathological classification of lymphomas is based on morphology and cell immunology. The updated classification system according to Lennert (Kiel) has been adopted in Germany and was recently modified to reflect the WHO classification. The definitions of stages I–IV in NHL agree with the Ann Arbor classification for Hodgkin’s disease.

Table 6a Classification of non-Hodgkin: comparison of the relevant classes in the Kiel and WHO classifications

Theml, Color Atlas of Hematology © 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.