Chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL)

Definition

A neoplasm of small round B-lymphocytes in the peripheral blood, bone marrow and lymph nodes, admixed with prolymphocytes and paraimmunoblasts (pseudofollicles), usually expressing CD5 and CD23. SLL is applied to those cases non-leukaemic with the same morphology

Synonyms

Epidemiology

B-CLL constitutes 90% of cases of chronic lymphoid leukaemia. Most patients are more than 50 years old, with a male predominance of 2:1.

Clinical features

Typical sites of involvement are lymph nodes, liver, spleen, skin, breast and ocular adnexa. Patients are commonly asymptomatic but may present with fatigue, autoimmune haemolytic anaemia, infections, hepatosplenomegaly or extranodal infiltrates.

Histopathology

The nodal architecture is replaced by a pseudofollicular pattern of pale areas composed of larger cells in a darker background of small cells. The pseudofollicles (proliferation centres, growth centres) contain a continuum of small, medium (prolymphocytes) to large (paraimmunoblasts) cells. The spleen shows predominantly white pulp involvement; pseudofollicles are less prominent. Some cases show plasmacytoid differentiation. Bone marrow involvement may be nodular, interstitial, diffuse or mixed. A paratrabecular distribution is not typical. Pseudofollicles are not common but may be found.

Immunohistochemistry

CD5	usually positive
CD10	negative
CD11c	positive (weak)
CD19	positive
CD20	positive (weak)
CD22	positive(weak)
CD23	usually positive
CD38	may be positive in cases with unmutated Ig variable region genes
CD43	positive
CD79a	positive
cyclinD1	negative
SIg	weak
FMC7	negative

: fresh frozen tissue only

Scoring system for immunophenotype

	CLL	score	other B-cell lymphoma	score
SIg	weak	1	strong	0
CD5	positive	1	negative (except mantle cell)	0
CD23	positive	1	negative	0
CD79a/CD22	weak	1	strong	0
FMC7	negative	1	positive	0
	CLL score 4 or 5		usual score 0 to 2

Variants

CLL or SLL with cleaved cells
Large-cell rich CLL or SLL
Mixed CLL (so-called by the FAB group) have small numbers of prolymphocytes (<10%) but retain the immunophenotype of CLL (SIg+, CD20+, CD5+, CD23+)¹.
B cell prolymphocytic leukaemia
- The prolymphocytes show variable staining for CD5 and CD23 and are usually CD25 negative¹.
Prolymphocytic transformation of CLL
- These cases show >55% prolymphocytes, but a recognisable population of small lymphocytes is usually retained. CD5 positivity is usually retained¹.
Richter's syndrome - transformation to diffuse large B-cell lymphoma - occurs in 3.5% of cases.
Hodgkin's disease variant of Richter's syndrome, occurs in 0.5% of cases.
- The Reed-Sternberg cells are CD15 positive and may be CD20 positive. There may be scattered Reed-Sternberg cells in a background of CLL or discrete areas of classical Hodgkin lymphoma.
Mu heavy chain disease: a defective mu heavy chain lacks a variable region. This is an extremely rare disease of adults with hepatosplenomegaly but lacking lymphadenopathy. The bone marrow contains characteristic vacuolated plasma cells admixed with small lymphocytes. The cells are CD5-, CD10-. The unbound light chain are found in the urine as Bence Jones proteins in 50% of cases. It is only slowly progressive.

Differential diagnosis

Other low grade non-Hodgkin's lymphomas: immunophenotypes

Prognosis

Incurable but with a very variable prognosis, CLL is often indolent, with a median survival of 7 years. ZAP-70 positivity, CD38 poisitivity and unmutated IgV(H) are all asociated with an inferior prognosis.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas Current Diagnostic Pathology 2000;6:55-63.

¹EJ Schlette. B-cell prolymphocytic leukaemia. Pathology Case Reviews 2000;5 (5):274-280.