Due to the similarities among lymphoproliferative disorders, it is often difficult to diagnose patients. Immunophenotyping helps distinguish B-PLL from similar diseases, one of its key identifiers is the absence in expression of the surface antigens CD10, CD11c, CD25, CD103 and cyclin D1 – an important regulator of cell-cycle progression.A case has been described as CD20+, CD22+, and CD5-.It can also be CD5+.Another case was described as CD45+, CD19+, CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. Cytogenetics
B-PLL is rare, consequently few genetic studies have focused on this disease. As a result, the associated genetic lesions underlying B-PLL are largely unknown. Chromosomal Mutations
The most commonly reported abnormalities have occurred at chromosome 14, specifically in a region of the chromosome called band q23 (14q23). Translocations to this location lead to overexpression of the cyclin D1 gene which has been linked to both the development and progression of a number of cancers. Other chromosomal abnormalities have been reported on 6q21, 11q23, 12p12, 13q14 and 17p.It can involve deletions from chromosome 11 and chromosome 13. TP53 Gene
Among the documented studies, mutations to the TP53 gene have occurred in 75% of all cases of B-PLL. This is the highest incidence among all sub-types of B-cell malignancies. Mutations to this gene have also been documented in other hematologic malignancies.TP53 is an important transcriptional activator of genes involved in the regulation of the G1 checkpoint of the cell cycle as well as certain genes responsible for programmed-cell death (apoptosis).
Generally, prolymphocyte proportion exceeds 90%
Minimal or absence of lymphadenopathy – abnormalities in size, number or consistency of lymph nodes
Splenomegaly - Abnormal enlargement of the spleen
High white blood cell count
B-symptoms – Fever, night sweats and/or weight lossSimilar to other leukemias, B-cell prolymphocytic leukemia is often asymptomatic. The most common signs and symptoms are the result of the inability of the bone marrow to produce normal levels of blood cells:
Anaemia – due to lack of red blood cells
More frequent, severe and prolonged infections – due to lack of normal white blood cells
Bleeding and bruising – due to lack of platelets

Diagnosis
Diagnosis of B-PLL is difficult due to its considerable overlap with other mature B-cell leukemias and lymphomas. It requires integration of morphology with diagnostic tests including immunophenotyping and chromosome analysis (cytogenetics). Morphology
The malignant B cells are larger than average. In order to diagnose a patient with B-PLL, b-prolymphocyte composition of a patients blood cells must exceed 55%. High white blood cell counts – greater than 100 x 109/L  – are also indicative of B-PLL. B-prolymphocytes are characterized by:
Large size – approximately twice the size of a normal small lymphocyte
Round or oval-shaped nuclei
Single prominent nucleolus
Moderately condensed nuclear chromatin
High nuclear-cytoplasmic ratio – indicates more abundant cytoplasm

Immunophenotype
This technique is used to study proteins expressed in cells using immunologic markers. In B-PLL patients there is strong expression of surface immunoglobulin – a membrane-bound form of an antibody, b-lymphocyte surface antigens CD19, CD20, CD22, CD79a and FMC7, and weak expression of CD5 and CD23.