Subtypes of Prolymphocytic Leukemia According to the Latest ICC Classification
The International Consensus Classification (ICC) recognizes two distinct subtypes of prolymphocytic leukemia: T-cell prolymphocytic leukemia (T-PLL) and B-cell prolymphocytic leukemia (B-PLL), though the status of B-PLL as a distinct entity remains highly controversial 1, 2.
T-Cell Prolymphocytic Leukemia (T-PLL)
T-PLL is firmly established as a distinct mature T-cell neoplasm with standardized diagnostic criteria 3.
- T-PLL represents a rare, aggressive mature T-cell malignancy with heterogeneous clinical presentation 3.
- The entity formerly called "T-CLL" has been reclassified as T-cell prolymphocytic leukemia in modern classification systems 4.
- International consensus criteria for T-PLL diagnosis, staging, and treatment response have been established by the T-PLL International Study Group (TPLL-ISG) 3.
- T-PLL is characterized by genetically complex features with a well-defined molecular landscape 1.
B-Cell Prolymphocytic Leukemia (B-PLL)
B-PLL's recognition as a distinct entity is currently under debate, with its de novo presentation removed from the upcoming WHO 5th edition classification 2, 5.
- B-PLL was recognized as a distinct entity in the WHO 4th edition (WHO-HAEM4), but this designation has been challenged 2.
- The diagnosis requires >55% prolymphocytes in the blood to distinguish it from chronic lymphocytic leukemia (CLL) 4.
- Recent investigations reveal substantial biologic and molecular heterogeneity within B-PLL cases 5.
- Many cases previously classified as B-PLL show similarities with other small B-cell lymphomas or represent prolymphocytoid transformation of existing lymphomas 5.
- Epigenetic studies suggest B-PLL may be distinct from CLL, mantle cell lymphoma, and splenic marginal zone lymphoma, with two potential epitypes showing different clinicobiological characteristics 6.
Key Diagnostic Distinctions
The critical morphologic threshold distinguishing these entities from CLL is the percentage of prolymphocytes:
- CLL may contain prolymphocytes comprising up to 55% of blood lymphocytes 4.
- Finding prolymphocytes exceeding 55% favors a diagnosis of prolymphocytic leukemia (B-cell PLL) 4.
Important Caveat
The controversy surrounding B-PLL centers on whether cases currently diagnosed as B-PLL represent a unique biologic entity or merely a morphologic transformation state shared by various small B-cell lymphomas 5. This has led to B-PLL becoming an extremely rare diagnosis, with most recent studies conducted on limited cohorts that preclude robust conclusions 5.