Separate clones in concomitant multiple myeloma and a second B‐cell neoplasm demonstrated by molecular and immunophenotypic analysis

Abstract

The occurrence of multiple myeloma (MM) and a second B‐cell neoplasm in the same patient is a rare event. We present 2 such patients, and provide evidence to support the presence of separate clones in these coexisting neoplasms. In the first case, MM became evident 14 months after the diagnosis of chronic lymphocytic leukemia (CLL). In past reports, most occurrences of this association, when investigated, have been regarded to be biclonal disease processes; however, with few exceptions, most were documented by immunologic studies alone. To establish the clonality in our case of CLL with MM, we examined both immunophenotypic data obtained by standard two‐color flow cytometric analysis, and patterns of immunoglobulin gene rearrangement, using standard Southern analysis and hybridization with 32P‐labelled JH and JK probes. This provided evidence for the presence in this patient of two separate monoclonal populations of B cells, manifested as light chain restrictions and gene rearrangements which differed in blood (CLL) and bone marrow (MM) samples. In the second case, MM presented simultaneously with bone marrow lymphocytosis and abnormal peripheral lymphocytes. Clonality studies on blood were not done. Bone marrow B‐cell gene rearrangement studies, however, revealed the presence of three bands in the JK blot of significantly different intensities, suggestive of two monoclonal populations. A monoclonal population of small cells with surface B markers and surface IgM was demonstrated by flow cytometry, while a second population of larger cells with intracytoplasmic IgG matching the patient's serum monoclonal protein was detected by immunofluorescence microscopy. The results in these 2 cases expand previous findings of the rare association of MM with a second B‐cell neoplasm, and demonstrate the usefulness of molecular diagnostic investigation.

The Shreveport Myeloma Experience: Survival, Risk Factors and Other Malignancies in the Age of Stem Cell Transplantation

“…Second malignancies associated with multiple myeloma (MM) were observed many years ago, but most were reported as case studies [1,2,3,4,5,6,7,8]. In the past, secondary leukemias were more frequent among patients diagnosed with MM [1], although several cases of secondary solid tumors were also described [2].…”

Concomitant Presence of Two Distinct Clones of Chronic Lymphocytic Leukemia and Plasma Cell Myeloma in a Patient

“…Some case studies have provided evidence that both arise from a single clone [8,15]. On the other hand, some authors have concluded that chronic lymphocytic leukemia and multiple myeloma occurring concomitantly in a single patient arise from two separate clones [5,7,9,13]. The techniques applied by various authors include sequencing and study of heavy chain gene rearrangement in both the populations of lymphocytes and plasma cells or study of interphase FISH for clonal chromosomal abnormalities [3,6,10].…”

“…The multiparametric flow cytometry of the bone marrow specimen can give help in accurate and rapid diagnosis. Several pertinent questions have been raised in such cases as whether the B-cell chronic lymphocytic leukemia and multiple myeloma arise as a single clone or two separate clones presenting concomitantly previous studies have used various modalities, either FISH [3,6] or immunoglobulin gene rearrangement analysis [7][8][9] to investigate into this. We present here a case which showed concomitant involvement by chronic lymphocytic leukaemia and plasma cell myeloma.…”

Simultaneous Presentation of Waldenstr^|^ouml;m Macroglobulinemia and Multiple Myeloma: Multidisciplinary Diagnosis, Treatment and 30-Month Follow-up

“…The simultaneous occurrence of MM and chronic lymphocytic leukemia (CLL) seems to be the most frequent event. Sometimes, CLL is discovered incidentally in patients with newly-diagnosed MM, [7][8][9] while in other cases MM develops during the evolution of CLL. 7,[9][10][11][12] In turn, CLL may also occur during the evolution of MM.…”

“…Sometimes, CLL is discovered incidentally in patients with newly-diagnosed MM, [7][8][9] while in other cases MM develops during the evolution of CLL. 7,[9][10][11][12] In turn, CLL may also occur during the evolution of MM. lymphoma, 14 malignant renal lymphoma, 15 MALT lymphoma, 16 and mantle cell lymphoma 17 have been reported.…”