ABSTRACT
Introduction 458 Chronic lymphocytic leukemia 458 Clinical features 459 Morphologic features 459 Immunophenotype 460 Molecular genetics 460 Pathogenesis 460 Differential diagnosis 461 Prognosis 461 B prolymphocytic leukemia 462 Clinical features 462 Morphologic features 462 Immunophenotype 462 Molecular genetics 462 Pathogenesis 462 Differential diagnosis 462 Prognosis 462 T cell large granular lymphocytic leukemia 463 Morphology and immunophenotype 463 Molecular genetics 464
Pathogenesis 464 Differential diagnosis 464 Prognosis 464 T prolymphocytic leukemia 464 Clinical features 464 Morphology 464 Immunophenotype 465 Molecular genetics 465 Pathogenesis 465 Differential diagnosis 465 Prognosis 465 μ Heavy chain disease 465 Clinical features 466 Morphology 466 Immunophenotype and molecular genetics 466 Pathogenesis 466 Differential diagnosis 466 Prognosis 466 Key points 466 References 466
This chapter will cover a subset of the mature lymphoid leukemias of small lymphocytes including chronic lymphocytic leukemia (CLL), B prolymphocytic leukemia (B-PLL), T cell large granular lymphocyte leukemia (T-LGL), and T prolymphocytic leukemia (T-PLL). We will also cover the rare μ heavy chain disease. Other B cell leukemias and lymphomas of small lymphocytes such as hairy cell leukemia, splenic lymphoma with villous lymphocytes, other marginal lymphomas, mantle cell lymphoma, lymphoplasmacytic lymphoma and follicular lymphoma are covered in
Chronic lymphocytic leukemia is the most common leukemia in the Western world. The age-adjusted estimated annual incidence in the USA is approximately 3.4/100 000.1
The median age at diagnosis is approximately 65 years with a 2:1 male to female ratio. Chronic lymphocytic leukemia is an indolent leukemia with a disease course that can often span more than 15 years. In fact, many patients may die with their disease rather than from it. Effective therapies do exist that can induce remissions, but relapses inevitably occur. Thus, CLL is currently considered incurable in the
Patients present with lymphocytosis (greater than 5.0 109/L, by definition persistent for at least 3 months)2 and are often asymptomatic. Others may have symptoms relating to organ involvement (splenomegaly, hepatomegaly) or lymphadenopathy. Anemia and other cytopenias are often present due to immune hemolysis related to the leukemia or simple bone marrow replacement by leukemic infiltrates. Chronic lymphocytic leukemia may progress with increasing numbers of prolymphocytes in the blood or patients may experience transformation to a large cell lymphoma (Richter syndrome), heralded by a sudden change in symptoms or rapid localized lymph node enlargement. Staging systems such as the Rai or Binet staging systems are used to predict prognosis in CLL patients (Table 27.1).3,4 While these systems are useful in stratifying patients, predicting outcome in intermediate stage patients is still difficult. Much work has been devoted to identifying biologic predictors of disease outcome (to be discussed).
