Review Lays Out the Tough Task of Discerning T-cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia is rare and shares many features with other conditions. A new review article helps explain some of the tactics physicians can use to correctly identify it.

T-cell prolymphocytic leukemia (T-PLL) is a rare form of leukemia that is much less common than its B-cell counterpart, yet it can be challenging to diagnose.

In a new review article, John L. Frater, MD, of the pathology and immunology department of Washington University School of Medicine in St. Louis, explains the features of T-PLL, differential diagnosis considerations, and relevant laboratory findings related to the cancer. His article was published in the International Journal of Laboratory Hematology.​

Frater traces T-PLL back to 1973, when Catovsky and colleagues reported 4 cases of prolymphocytic leukemia, including one that appeared to be of a T-cell origin. The patient had some features similar to those with B-cell prolymphocytic leukemia, including prominent splenomegaly, peripheral lymphocytosis, and a lack of significant lymphadenopathy. However, the T-PLL patient’s malignant cells were negative for surface immunoglobulin, had a low number of cells with C3 receptors, and the patient prolymphocytes formed rosettes with sheep red blood cells.

Further research showed that the malignant cells of patients with T-PLL can be small and resemble the cells of B-chronic lymphocytic leukemia/small lymphocytic leukemia, leading some to diagnose the disease as T-cell chronic lymphocytic leukemia. However, subsequent investigation into the immunophenotypic, genetic, and clinical features led to the conclusion that T-CLL belonged under the category of T-PLL, Frater said.

Patients with T-PLL tend to be older, with a median age of 65 at presentation. The peripheral blood and spleen are commonly involved, as are peripheral lymph nodes, Frater said. The skin is involved in about 1 in 5 cases. The proposed major criteria for diagnosis are >1 x 109/L cells of PLL phenotype in the peripheral blood or bone marrow, T-cell clonality (as determined by polymerase chain reaction or flow cytometry), and abnormalities of 14q32 or Xq28 OR expression of TCL1A/B or MTCP1. Minor criteria include abnormalities involving chromosomes 11 and 8. Patients with the diagnosis have a median survival of 1-2 years, Frater reported.

Diagnosing T-PLL involves differentiating the disease from other conditions with peripheral lymphocytosis, splenomegaly, and skin involvement.

“Distinction among entities with these presenting features may be challenging and often relies on an in-depth knowledge of clinical findings, morphologic and immunophenotypic features, and molecular genetic findings,” Frater said, before explaining some of the features in more depth.

For laboratory professionals, Frater said there are a number of factors to be aware of, since there is generally no single feature that enables a clear identification of T-PLL.

He said splenomegaly is usually the most common physical finding at diagnosis of T-PLL, though lymphadenopathy is also common. When the skin is involved, patients with T-PLL tend to have a papulonodular pattern, in contrast to Sézary syndrome, which tends to involve a diffuse erythematous rash.

T-PLL often includes marked peripheral lymphocytosis, Frater reported, and distinguishing features can be found in the appearance of malignant cells in the blood and other areas.

“The cells in T‐PLL are most commonly small‐ to medium‐sized with variably prominent nucleoli,” Frater wrote. “However, in up to 25% of cases, the cells are small and mature-appearing without nucleoli, resembling resting lymphocytes or chronic lymphocytic leukemia cells.”

Flow cytometry can also be helpful in arriving at the correct diagnosis. In about one-quarter of cases, flow cytometry shows “a mature (ie, CD45 bright) T-cell population which coexpresses CD4 and CD8, which can be extremely helpful in establishing the diagnosis, as this immunophenotype would not be expected in most of the entities in the differential diagnosis.”

Frater said in the majority (80-90%) of cases of T-PLL, molecular genetic analysis will reveal an inversion of the long arm of chromosome 14, which can help confirm the diagnosis. This can usually be identified with fluorescence in situ hybridization probes, he said.

In summary, Frater said T-PLL shares many features with other potential diagnoses. He said clinical presentation features can be helpful in arriving at the correct diagnosis, but added that “the clinical laboratory plays a central role in the diagnosis of T-PLL and detecting biomarkers determining disease outcome.”


Frater JL. T-cell prolymphocytic leukemia: Review of an entity and its differential diagnostic considerations. Int J Lab Hematol. 2020;42 Suppl 1:90-98. doi:10.1111/ijlh.13180

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