Diagnosis of<unk>  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<unk> s are larger than average. In order to diagnose a patient with<unk> , b-prolymphocyte composition of a patient's blood<unk> s must exceed 55%. High white blood<unk>  counts – greater than 100 x 109/L – are also indicative of<unk> . 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<unk> s using immunologic markers. In<unk>  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. Due to the similarities among lymphoproliferative disorders, it is often difficult to diagnose patients. Immunophenotyping helps distinguish<unk>  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<unk> -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<unk>  is rare, consequently few genetic studies have focused on this disease. As a result, the associated genetic lesions underlying<unk>  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<unk> . 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<unk>  cycle as well as certain genes responsible for programmed-cell death (apoptosis). It is believed that mutations to TP53 are responsible for the frequent therapy resistance and aggressive course of this disease. c-MYC Gene In a small number of<unk>  cases, abnormalities in the c-MYC gene have been observed. It is considered a global amplifier and influences nearly all aspects of<unk> ular activity. Among the number of genes it regulates, most are involved in<unk>  growth,<unk>  cycle progression, protein biosynthesis and apoptosis. Amplification of c-MYC has been reported in<unk>  patients and while the consequences are unclear, it is generally associated with poor clinical outcome. Biopsy After physicians have identified an abnormality in the composition of the peripheral blood, biopsies (tissue samples) from a patient's bone marrow and/or spleen are often recommended for confirmation. A bone marrow biopsy involves the removal of a small amount of tissue that is further analyzed for abnormalities, for<unk>  pathologists look for prolymphocytic infiltration where the hematopoietic stem<unk> s of the bone marrow are replaced with prolymphocytes due to excess production. In 50% of reported cases, it was common for patients to be both anemic (lack healthy red blood<unk> s in blood) and thrombocytopenic (deficiency of platelets in blood).
B-cell prolymphocytic leukemia
Aggressive NK-cell leukemia
T-cell prolymphocytic leukemia
Precursor B-cell lymphoblastic leukemia
T-cell acute lymphoblastic leukemia
T-lymphoblastic leukemia/lymphoma
Acute myeloblastic leukemia with maturation
Acute myeloblastic leukemia without maturation