Utility of Bone Marrow Biopsy, Bone Marrow Aspirate, Flow Cytometry, and Molecular Testing in the Clinical Staging of Lymphoma: An Institutional Experience.

Lymphomas are a diverse group of solid tumors of lymphoid cells that are broadly subdivided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) categories. In the Western world, lymphoma is the most common hematologic malignancy. Complete and accurate staging of the patient with lymphoma is essential in determining the extent of initial disease. Bone marrow biopsy (BMB) remains the gold standard for assessing bone marrow involvement by lymphoma. It allows morphological diagnosis as well as the use of immunohistochemistry in difficult cases. At the time of BMB, other specimens are often gathered for use in ancillary investigations that can aid in diagnosis and/or staging. These investigations include bone marrow aspirate (BMA), flow cytometry (FC), and molecular studies (M) such as PCR. The objectives of this study were to evaluate the performance characteristics of BMA, FC, and M relative to BMB in lymphoma staging, to determine how frequently ancillary testing is positive for bone marrow involvement with lymphoma while BMB is negative, as well as to determine the clinical significance of this situation. Retrospective analysis was performed on 294 lymphoma cases from 1997 to 2002 at a single adult tertiary care center. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), pre-test probability (PreTP), post-test probability given a positive test result (PTP+), and post-test probability given a negative test result (PTP−) were determined. Chart review was performed to determine clinical significance of the situation when BMB is negative and one or more ancillary investigations are positive. The number of cases positive for lymphoma by BMB, BMA, M, and FC was 157,113, 109, and 111, respectively. The performance characteristics are indicated in Table I. Twelve cases in which one or more ancillary investigations were positive when BMB was negative were identified. Clinical management was not altered in these cases. In staging of lymphoma, BMB remains the gold standard for the determination of bone marrow involvement. When compared to BMB, ancillary investigations have a high specificity and PPV, but only moderate sensitivity and NPV. Ancillary bone marrow investigations appear to add little information to lymphoma staging, and may not be fiscally justified.