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For most malignancies, diagnosis is the domain of the histopathologist, and prognosis the province of the clinician. However, the haematopathologist has something to contribute in distinguishing different forms of low-grade lymphoproliferative diseases, especially when these reside mainly in the blood and bone marrow, and, thanks to new techniques in molecular biology and cytogenetics, can override the prognostications of the physician, who can only determine how much disease is present.


At one time, excessive lymphocytes in blood signified lymphatic leukaemia, which was divided on morphological grounds into acute and chronic depending on whether the cells were blast-like or not.


On the basis of the presence of immunoglobulin molecules on the cell surface or reactivity with anti-CD3, lymphoid malignancies are diagnosed as B cell or T cell, and the practice of calling chronic lymphocytic leukaemias (CLL) either B-CLL or T-CLL evolved. This should now be unnecessary as T-CLL has disappeared from classifications. All cases of CLL are B-CLL and the B has become superfluous. In the past, series of patients with CLL have included cases with other diagnoses. The most commonly mistaken alternative diagnoses are splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), the CLL – prolymphocytic leukaemia (PLL) interface, and small cell versions of some T-cell leukaemias, notably T-PLL and Sezary syndrome.

The immunophenotypes of the different lymphoid tumours that often present with a lymphocytosis are shown in Table 3.1. CLL cells express surface immunoglobulin, usually IgM plus IgD. The number of immunoglobulin molecules is only about 10% of those on normal B cells, so the staining is usually weak to moderate. The immunoglobulin-associated molecule Igβ or CD79b is similarly reduced in quantity and is generally weak or absent. CD20 is present, but again the staining is weaker than on normal B cells. FMC7 is an antibody that detects an epitope of CD20 that is not exposed in CLL. FMC7 is usually weak or absent on CLL cells. The cells are CD19 positive, but unlike most B cell lymphomas they are also CD5 positive. CD22 is a ubiquitous B-cell antigen, but in CLL it tends to be present not on the cell surface, but only in the cytoplasm. Finally, CD23, the Fcε receptor, is expressed on CLL cells unlike other B-cell malignancies. In biology nothing is absolute, and cases of atypical CLL are fairly common. To help elucidate these difficulties, The Royal Marsden Hospital (Sutton, Surrey, UK) has introduced a scoring system [1] (Table 3.2).

Table 3.1Typical immunophenotyping of the low and some intermediate grade B and T cell lymphoproliferative disorders

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