Molecular assessment of clonality in lymphoid neoplasms

Molecular clonality assays in B- and T-cell lymphoproliferative disorders often provide critical information in establishing a diagnosis of a lymphoproliferative disorder. These assays rely on the unique genetic structures that serve as assay targets, created in the process of generating immunoglobulin and T-cell receptors during B- and T-cell development. Molecular clonality assays are generally used when flow cytometry or immunohistochemistry has not sufficiently clarified the benign or malignant nature of a lymphoid proliferation. Additionally, since molecular clonality assays are tumor specific, they allow the clinician to distinguish recurrences from second tumors, and have the sensitivity to monitor minimal residual disease. In this review, we discuss the principles underlying these tests, the current approaches to clonality testing, some of the pitfalls in their interpretation, and the future applications of next generation sequencing technology to clonality testing.