• 2018-07
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  • 2018-11
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  • 2019-05
  • In a letter to the editor


    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 LY 2109761 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.
    Case Twenty years prior to presentation to us, a 39yr-old female had a transient ischemic attack (TIA), and based on abnormal laboratories, was diagnosed with polycythemia vera (PV). She developed multiple thrombotic complications, including myocardial infarction, cerebral vascular accident and an aortic valve thrombus. She was initially managed with phlebotomy for 4 years, followed by hydroxyurea for approximately 14 years. Seventeen years into her illness, progressive massive splenomegaly necessitated splenectomy. Recombinant erythropoietin was started 18 years into her illness, followed by periodic red blood cell (RBC) transfusions to treat progressive anemia. Twenty years after her initial PV diagnosis a bone marrow biopsy specimen confirmed post-PV MF. Four months later, she was started on thalidomide 50mg daily and prednisone 0.5mg/kg, reducing this dose by 50% over the next 2 months. Her physical exam was notable for tachypnea, scleral icterus, hepatomegaly and lower extremity pitting edema. Admitting laboratories demonstrated leukocytosis with a white blood cell count (WBC) of 68.9×109/L, with a differential of 18% neutrophils, 2% lymphocytes, 5% monocytes, 69% eosinophils (absolute eosinophil count of 47.5×109/L), and 1% basophils. Rare blasts, metamyelocytes, and myelocytes were noted. She required RBC and platelet transfusion support through the course of her hospitalization. The hepatic transaminases were normal, but the bilirubin was 5.2mg/dL (direct 2.4mg/dL), and her prothrombin time was prolonged at 16.1s. Other pertinent labs included a lactate dehydrogenase of 1453units/L, and an increased troponin I of 2.2ng/mL.