Immunophenotypic and immunogenotypic approaches useful in distinguishing benign and malignant lymphoid proliferations.

Distinguishing benign and malignant lymphoproliferative disorders by purely morphologic criteria can be difficult. Immunophenotypic analysis is a useful adjunct to the morphologic evaluation of lymphoproliferative disorders and is of considerable assistance in resolving difficult diagnostic dilemmas. Immunophenotypic analysis can be performed on virtually any pathologic specimen using a variety of methodologic approaches. The analysis should be tailored to the individual pathologic specimen and the specific diagnostic problem. The results should be correlated with the clinical and morphologic findings. Southern blot hybridization analysis of the antigen receptor genes has proven to be an objective, accurate, and sensitive method by which to determine the lineage and clonality of lymphoid proliferations and to detect clonal B- and T-cell populations that are not recognizable morphologically or immunophenotypically. Polymerase chain reaction-based strategies extraordinarily more sensitive than Southern blotting are currently being developed. However, the demonstration of clonal antigen receptor gene rearrangements is an indication of clonality and not necessarily of malignancy, although the two are closely related. This and all the other biologic and technical limitations of immunogenotypic analysis must be considered when evaluating the results of such studies. Ideally, the results of immunogenotypic analysis should be interpreted only in conjunction with the results of morphologic evaluation and immunophenotypic analysis.