A yr old female with no significant past medical history

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 order Calcium Ionophore I 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. In a letter to the editor of , Dasanu reported the case of a 55-yr-old male diagnosed with t(11;14)+ IgG-lambda MM, who presented with enlarged lymph nodes six years later. Biopsy was consistent with CD5-negative MCL. In 1999, Yamaguchi conducted clonal relationship analysis on myeloma and lymphoma cells obtained from a 76-yr-old male diagnosed with CD5-positive MCL and IgG-kappa MM. He concluded that there was no clonal relationship between the two diseases. However, a recent study of seven MCL cases presenting with a plasma cell component demonstrated that in five patients both MCL and plasma cell clones had identical restriction fragments, and thus a common clonal origin. In addition to the fact that both diseases arise from B cells, these two malignancies also share some other features including the presence of t(11;14) and the overexpression of cyclin D1. It is suggested that overexpression of this important cell cycle regulator is crucial for malignant cell survival in MCL; on the other hand, the importance of t(11;14) in the pathogenesis of MM remains uncertain. Some investigations concluded that cyclin D1 expression was not essential for the pathogenesis of MM. For example, Fiancette et al. showed that deregulation of CCND1 gene and overexpression of cyclin D1 did not result in accelerated tumorigenesis in mice; thus, concluding that cyclin D1 expression may simply represent a “single hit” in B-cell malignancies and may not in itself be adequate for oncogenesis. However, Marsaud and her partners injected cells that had been genetically modified to express cyclin D1 into immunocompromised mice to test the oncogenic property of this factor. The mice developed malignant tumors at the injection site demonstrating that cyclin D1 is indeed oncogenic. In fact, another animal study also illustrated the oncogenic nature of cyclin D1 expression and proposed a possible mechanism through its nuclear-retention. More recently, Tchakarska and colleagues showed that cyclin D1 might also act by inhibition of mitochondrial metabolism which could potentially lead to loss of apoptosis and, therefore, uncontrolled growth. It is important to point out that although the t(11;14)(q13;q32) can be present in both MCL and MM; the genetic background is different. In the first, the translocation results from VDJ recombinations, and in the later, it is the product of errors in somatic hypermutation within the IgH switch regions. Unfortunately, molecular studies of the cancer cells for clonal relationship could not be undertaken in our patient because of lack of adequate MCL sample. Sequencing of the IgH regions from the two cell groups would have been very informative. It is however interesting to speculate about a possible composite disease based on multiple facts; the CD19 negativity which is uncommon in pure plasma cell dyscrasias; high M-spike and other features of multiple myeloma, but poor response to bortezomib as sometimes seen in MCL.