The deletion of q seen in
The deletion of 14q seen in our patient included the IGH locus at 14q32.33. This is noteworthy, because loss of 14q has been reported as a recurrent aberration acquired during the natural history of CLL. The acquisition of a del(14) may thus be indicative of CLL in transformation. In a study of a large German cohort, del(14q) was found in ∼2% of newly diagnosed CLLs, and these patients typically required more immediate therapy. The investigators used a panel of 14q probes to determine that the del(14) was usually interstitial and heterogeneous in size, with a breakpoint cluster at the centromeric site in 14q24.1; in most cases the breakpoint at the telomeric site was within the IGH locus while ∼25% showed a deletion of the entire IGH locus, as was the case in our patient.
Conflict of interest
Acknowledgments We thank Yu Cao, MS, for technical assistance with the DNA copy number assay. This study was supported by the National Cancer Institute Award CA-06927 and an appropriation from the Commonwealth of Pennsylvania. The Genomics Facility of Fox Chase Cancer Center shared facility was used in the course of this work. The study sponsors had no involvement in the study design, collection, analysis and interpretation of data.
Multiple myeloma and mantle cell lymphoma are well defined B-cell malignancies with significant disease burden worldwide. Understanding of the pathogenesis of both entities has improved over the years, leading to new therapies and improved survival rates. The hallmark of MCL is t(11;14)(q13;q32); this genetic alteration leads to overexpression of Staurosporine D1, an important regulator of the cell cycle. While the same translocation and overexpression of cyclin D1 has been recognized in a subset of patients with MM, its role in the pathogenesis of myeloma is still undetermined. The occurrence of MCL and MM in the same patient is very rare. To our knowledge, there are only limited case reports of MCL and MM affecting the same patient. Here we report a case of MM which arose in a patient previously diagnosed and successfully treated for MCL. We also review literature to explore the relationship, if any, between these two entities to understand how genetic factors might contribute to their development in a single individual. A 64yr-old female with no significant past medical history developed lymphadenopathy and splenomegaly in the 1970s. By patient report, all pathology studies obtained following splenectomy were negative for malignancy. In 2003 the patient presented again with generalized lymphadenopathy. A diagnosis of MCL was made; the bone marrow was not involved. After six cycles of cladribine and rituximab, the disease went into remission for four years. In 2007, routine follow-up imaging demonstrated recurrence of lymphadenopathy. An axillary lymph node biopsy was again positive for a monoclonal B cell population characteristic of MCL. Flow cytometry confirmed a clone expressing CD5, CD19, CD20, FMC-7 and kappa light chain. FISH confirmed a CCND1/IgH rearrangement in 63% of cells. There was no evidence of a plasma cell component. The patient completed six cycles of bortezomib, pentostatin, and rituximab. She was then placed on maintenance therapy with rituximab every three months until September 2010. Shortly after her last dose of rituximab she developed generalized body aches, fatigue, headache, dizziness, and epistaxis. Physical examination was unremarkable except for right tonsillar prominence. Extensive laboratory studies revealed normocytic anemia, mild hypercalcemia, elevated total protein, high serum viscosity, and normal renal function. Special protein studies showed a monoclonal IgM kappa protein, an M-spike of 4gm/dL and IgM of 7060mg/dl. Plasmapheresis was started for hyperviscosity syndrome. PET/CT scan showed no diffuse lymphadenopathy or bony lesion; there was a 2-cm mass in the right palatine tonsil region with increased FDG uptake. Biopsy was planned, and then canceled given increased risk of bleeding due to high serum viscosity. Bone marrow aspiration and biopsy showed a hypercellular marrow (60%) with 50% clonal plasma cells consistent with multiple myeloma. There was no evidence of mantle cell lymphoma or lymphoplasmacytic lymphoma. Repeat studies by different institutions confirmed kappa light chain positive myeloma with negative immunostaining for CD5, CD19, CD20, and CD56. Cytogenetic studies revealed a 46, XX female karyotype and the presence of t(11;14) by FISH as the only genetic aberration. She had a good response to therapy after receiving four cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD) with the M-spike dropping to as low as 1.2, quantitative IgM to 2060mg/dl, and plasma cells to only 10 % in the bone marrow. She underwent peripheral blood stem cell (PBSC) collection; 6 million CD34+ cells were collected after administration Plerixafor in addition to high dose G-CSF. Additional three cycles of VCD were given, then cyclophosphamide was replaced by lenalidomide due to poor response. After four cycles of VRD the patient underwent successful autologous PBSCT. Both MM and MCL are currently in remission.