title: Extranodal diffuse large B-cell lymphoma with monoclonal gammopathy: an aggressive and primary refractory disease responding to an immunomodulatory agent.
abstract: BACKGROUND
  Although the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) has been improved by the addition of rituximab to standard chemotherapy, almost one-third fails or relapses after first line treatment. The presence of monoclonal gammopathy (MG) is a known adverse prognostic factor for DLBCL. Because this subset of patients does not benefit from R-CHOP, new therapeutic options are required. Herein, we report the first case of extranodal DBCL of the lung with a concomitant MG who achieved a long lasting complete remission with lenalidomide.
  
  
  METHODS
  The 73-year-old male patient presented with lateral cervical lymphadenopathy, B symptoms, lactate dehydrogenase and beta2-microglobulin elevation. Computed tomography (CT) showed mediastinal lymphadenopathy and bilateral lung involvement. Biopsy of both disease locations revealed the presence of DLBCL. Successive bone marrow trephine biopsy proved the presence of concordant DLBCL involvement. At the time of diagnosis, a MG was present as well. The patient did not respond to the standard treatments, and subsequently underwent lenalidomide 25 mg/m(2) days 1-21 q28 plus dexamethasone 40 mg days 1-4, 9-12 e 17-20. This therapeutic regimen was efficacious and safe as salvage therapy in extranodal DBCL with a MG. Furthermore, we observed a close association between DLBCL response to therapy and MG levels, suggesting that the amount of M-protein might be a surrogate marker of disease response.
  
  
  CONCLUSIONS
  Although DLBCL associated with MG does not respond properly to the standard treatments, it is highly sensitive to lenalidomide, which is why we endorse its role as treatment of choice in this subset of patients. In addition, MG levels appear to correlate with tumor burden, suggesting that it might be a useful marker of disease response. Prospective trials to validate these observations are warranted.
authors.affiliation: Department of Human Pathology, University of Messina, Via Consolare Valeria, 98100 Messina, Italy ; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy ; Lymphoma Department, Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY USA.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondello
authors.affiliation: Department of Human Pathology, University of Messina, Via Consolare Valeria, 98100 Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pitini
authors.affiliation: Department of Human Pathology, University of Messina, Via Consolare Valeria, 98100 Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, New York, NY USA ; Weill Cornell Medical College, New York, NY USA.
authors.forename: Elliott Joseph
authors.initials: EJ
authors.lastname: Brea
authors.affiliation: Department of Human Pathology, University of Messina, Via Consolare Valeria, 98100 Messina, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Di Mirto
authors.affiliation: Department of Internal Medicine, University of Messina, Messina, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Arrigo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Hematology and CBMT, Ospedale di Bolzano, Bolzano, Italy ; Universitätsklinik für Innere Medizin V, Hämatologie and Onkologie, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mian
keywords: Diffuse large B-cell lymphoma; Lenalidomide; Monoclonal gammopathy; Serum free light chain