title: Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies.
abstract: The coexistence of multiple myeloma (MM) and mycosis fungoides (MF), and hence of both B- and T-cell neoplastic clones, is a rare event. We describe a case of plaque-stage MF associated with IgG lambda MM. The clinical onset of MF preceded that of MM, supporting the hypothesis that MF predisposed to the development of the B-cell proliferative disorder. The skin tumor cells were found to originate from CD4(+) T-lymphocytes, characterized by a V beta 8 receptor and no proviral human T-lymphotropic virus (HTLV)-I monoclonal integration. They also displayed a polarized Th1-type cytokine profile containing mRNAs for interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta, but not for IL-4, IL-5, or IL-10. The CD8(+)/CD57(+) suppressor-cytotoxic subpopulation was significantly increased in the peripheral blood and was associated with MM progression. Expression of p16INK4A, a gene from the INK family that inhibits cyclin-dependent kinases and regulates the cell cycle, was lacking in MF cells and bone marrow (BM) plasma cells. The p16INK4A gene was silenced by hypermethylation, suggesting that it plays a role in the early phase of the pathogenesis of both diseases. Thus, a lymphoid precursor cell presumably contains aberrations that induce the development of both clonal diseases in a multistep process.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Section of Internal Medicine and Clinical Oncology, Piazza G. Cesare, 11, 70124 Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gernone
authors.forename: M A
authors.initials: MA
authors.lastname: Frassanito
authors.forename: A
authors.initials: A
authors.lastname: Pellegrino
authors.forename: A
authors.initials: A
authors.lastname: Vacca
authors.forename: F
authors.initials: F
authors.lastname: Dammacco
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000235:genetics / Q000276:immunology; D009182:Mycosis Fungoides / Q000150:complications* / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D012313:RNA / Q000032:analysis; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016207:Cytokines; D012313:RNA