Pathophysiology

The reason that some patients present with PCL and others have evolvement to it is unclear. Primary PCL is a distinct entity because its presenting features, response to chemotherapy, and survival are different from those in multiple myeloma. In patients with primary PCL who respond to chemotherapy, PCL almost always reappears at relapse, whereas only 1% of patients with multiple myeloma evolve to a secondary PCL.30

Primary PCL cells have a higher expression of CD20 antigen than do cells from multiple myeloma.28 Plasma cells from both primary and secondary PCL usually lack CD56 antigen, which is important in anchoring plasma cells to the bone marrow stroma.31 One study showed that the expression of CD28 appears to differentiate primary from secondary PCL.31 In one report, more than 80% of patients with PCL were diploid or hypodiploid compared with 40% of patients with multiple myeloma, and 60% of patients with multiple myeloma were hyperdiploid (33). In another series, 17 of 20 (85%) patients were nonhyper-diploid, 2 were equivocal, and 1 was hyperdiploid.29

Cytogenetic studies show a complex karyotype with multiple structural and numeric abnormalities in most cases. Fluorescence in situ hybridization showed monosomy of chromosome 13 in 12 of 13 patients.28 In contrast, cytogenetic findings associated with a favorable outcome such as trisomy of chromosomes 6, 9, and 17 are absent in primary PCL.28 In a report of 20 patients with PCL (13 primary and 7 secondary), 15 had IgH translocations. Two-thirds of the translocations were t(11;14)(q13;q32), which is an unfavorable prognostic feature. Fourteen patients (70%) had deletion of chromosome 13, whereas 10 had t(17;p13.1) (p53 locus), which are both unfavorable prognostic features.

Mutations of N- and K-ras oncogenes have been reported in up to 58% of patients with PCL.32 33 Amplification of the c-myc oncogene at the DNA level with concomitant overexpression has been reported.34 In two series, 4 of 12 (33%) and 3 of 10 (30%) patients with PCL had p53 mutations.33 35 Hypomethylation of p16 has been reported in PCL.36

Interleukin 6 (IL-6) is the major plasma cell growth factor in vitro and in vivo in patients with multiple myeloma.37 In a series of 13 patients with PCL, all had significant spontaneous cell growth after 5 days in culture and all had significant growth when stimulated with exogenous IL-6.38 The role of IL-6 is supported by blockage of plasma cell proliferation when treated with anti-IL-6 monoclonal antibody.39

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