Chapter 67: Mature T-Cell and Natural Killer Cell Lymphomas

CLASSIFICATION

• The lymphomas of mature T cells and natural killer (NK) cells are shown in Table 67–1. The cutaneous forms are discussed in Chap. 66.

T-CELL LEUKEMIAS

T-Cell Prolymphocytic Leukemia

• Prolymphocytes (large [T] lymphocytes usually with prominent nucleoli) represent at least 50 percent of lymphocytes in the blood. They often have nuclear convolutions.

• T-prolymphocytes characteristically express pan-T-cell markers: CD2, CD3, CD5, and CD7.

• In the majority of cases, prolymphocytes express CD4 but not CD8 (i.e., malignant cell of T-helper cell origin). In occasional morphologically identical cases, CD4 may be weakly expressed or absent and CD8 may be weakly positive. CD52 is highly expressed and can be a target of therapy.

• Inversion of chromosome 14 is the most common cytogenetic abnormality and is found in 80 percent of patients. The t(14;14) occurs in 10 percent of patients. Associated abnormalities of chromosome 8 (e.g., t(8;8)) are common as well. Several other chromosomes (e.g., 6, 11, 17) may also be abnormal.

• Represents 20 percent of prolymphocytic leukemias; the remainder have a B-cell phenotype.

• The male:female ratio is 1.5:1.

• The tissue (e.g., lymphatic tissue) involvement and blood involvement coexist and are striking in both locations.

• Most patients have generalized lymphadenopathy and hepatosplenomegaly with marrow replacement and lymphoma cells dominating the white cell count (usually >100 × 10⁹/L).

• Anemia and thrombocytopenia are nearly always evident at diagnosis.

• Skin involvement occurs in approximately 20 percent of patients.

• Serology for the human lymphocytotropic virus-1 is negative.

• The clinical course is usually rapid. Median survival is less than 1 year.

• No standard chemotherapeutic treatment program has been developed. For example, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (Oncovin), prednisone (CHOP) therapy does not produced long-term remissions.

• Pentostatin and cladrabine can induce responses in approximately 40 percent of patients; but, complete remissions are infrequent (~10%) and long-term responses (>1 year) are uncommon.

• Alemtuzamab, a humanized monoclonal antibody against CD52, given three times weekly, has induced good responses in over 50 percent of patients.

• Allogeneic hematopoietic stem cell transplantation can induce a long-term remission of the disease.

• Occasional patients may have a chronic course of a few years but then evolve to a rapidly progressive phase.

T-Cell Large Granular Lymphocytic ...