T-cell prolymphocytic leukemia

Overview
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include: T-cell chronic lymphocytic leukemia, "Knobby" type of T-cell leukemia, T-prolymphocytic leukemia/T-cell lymphocytic leukemia

Clinical Features
Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow, spleen, liver, skin.

Etiology
It is postulated that the originating cell line for this disease is a mature (post-thymic) T-cell.

Clinical Presentation
Patients typically have systemic disease at presentation, including hepatosplenomegaly, generalized lymphadenopathy, and skin infiltrates.

Laboratory Findings
A high lymphocyte count (> 100 x 109/L)along with anemia and thrombocytopenia are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.

Morphology
In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilic cytoplasm with occasional blebs or projections. The nuclei are usually round to oval in shape, with occasional patients having cells with a more irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sézary syndrome. A small cell variant comprises 20% of all T-PLL cases, and the Sézary cell-like (cerebriform) variant is seen in 5% of cases.

Marrow involvement is typically diffuse with morphology similar to what is observed in peripheral blood. In the spleen, the leukemic cell infiltrate both the red pulp and white pulp, and lymph node involvement is typically diffuse through the paracortex. . Skin infiltrates are seen in 20% of patients, and the infiltrates are usually dense and confined to the dermis and around the skin appendages.

Immunophenotype
T-PLL has the immunophenotype of a mature (post-thymic) T-lymphocyte, and the neoplastic cells are typically positive for pan-T antigens CD2, CD3, and CD7 and negative for TdT and CD1a. The immunophenotype CD4+/CD8- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ immunophenotype is present in 15% of cases.

Genetic Findings
Clonal TCR gene rearrangements for the γ and δ chains are typically found. The most frequent chromosomal abnormality is the inversion of chromosome 14, specifcally inv 14(q11;q32). This is found in 80% of cases, while 10% of cases show a reciprocal translocation of chromosome 14 (t(14;14)(q11;q32)).

Also, abnormalities of chromosome 8 are seen approximately 75% of patients, including idic (8p11), t(8;8)(p11-12;q12), and trisomy 8.