2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia

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The evolution of flow cytometric immunophenotyping (FCI) from its early use as a biomarker of immune function in AIDS to a central role in the diagnosis of hematopoietic neoplasms and detection of minimal disease has brought it to the mainstream of clinical medicine. Because this evolution proceeded in research and clinical laboratories of pathology, it has resided on the clinician's horizon due to perceived inconsistencies in standardization, interpretation, and application. To help clarify the role of FCI in clinical practice, an international group of experts provide an important consensus report on the medical indications of FCI in hematological malignancies. From a clinician's vantage, FCI provides both insight and challenges. As a diagnostic tool, FCI has become a gold standard in acute and chronic leukemia and plays an important adjuvant role in lymphomas and other “solid” presentations of hematological diseases. In benign elevations of the white count, the etiology may be readily apparent such as steroids or may be less obvious and confused with a lymphoid leukemia in infectious mononucleosis or chronic myelocytic leukemia in a severe leukemoid reaction. Of course when considered within their medical context, FCI is infrequently indicated in these circumstances. Thus, the present consensus document aptly provides clinical guidance for both the treating clinician and pathologist on when FCI is and is not indicated under a variety of clinical settings. The high sensitivity of FCI makes it a particularly important tool for detection of low numbers of abnormal cells. Such sensitivity may be vital for discerning the cause of bone marrow aplasia or differentiating plasma cell myeloma from monoclonal gammopathy of undetermined significance. It may also be used during initial evaluation to upstage patients, which in the absence of prospective evaluation may lead to stage migration and improper treatment. Hence, like other new and highly sensitive staging tests, in the absence of prospective validation, treatment decisions should be appropriately considered. One such example is the use of FCI for detection of lymphoma in cerebral spinal fluid. Its high sensitivity has led to an increased detection rate significantly above conventional cytology and raises the question of their clinical significance. Although some clinicians might consider such findings commensurate with active disease, others might not treat aggressively. FCI is also useful for detection of minimal residual disease. Similarly, the therapeutic response to such findings needs to be carefully studied in prospective trials. The broad applications and sensitivity of FCI makes it one of the most powerful tools in the clinical pathology armamentarium, making the understanding of its use and limitations critical for the evaluation, and treatment of hematopoietic neoplasms. Indeed, the constantly expanding number and types of fluorescent probes will make FCI an increasingly powerful tool in the future.