MANTLE CELL LYMPHOMA Clinicopathological Features and Prognostic Factors

..................................................................................................... 10 INTRODUCTION ............................................................................................. 13 REVIEW OF THE LITERATURE ................................................................... 15 EVOLVING CLASSIFICATION OF NON-HODGKIN’S LYMPHOMAS ...................... 15 MANTLE CELL LYMPHOMA .............................................................................. 17 Background ................................................................................................... 17 Pathogenesis and biology ................................................................................ 17 Translocation (11;14)(q13;q32) and BCL1/CCND1 gene ........................... 17 Cyclin D1 protein and aberrant cell cycle function ................................... 18 Other cytogenetic and molecular changes ............................................... 19 Pathological characteristics ............................................................................. 22 Diagnosis and differential diagnosis of mantle cell lymphoma ............................ 23 Clinical manifestations ................................................................................... 24 Treatment results and prognosis ....................................................................... 24 Conventional treatment ....................................................................... 24 High-dose therapy with stem cell transplantations .................................... 27 Immunotherapy ................................................................................ 28 Factors related to outcome .............................................................................. 28 Tumour-related factors ....................................................................... 28 Patient-related factors ........................................................................ 29 AIMS OF THE STUDY .................................................................................... 31 PATIENTS, MATERIALS, AND METHODS .................................................. 32 Patients ......................................................................................................... 32 Evaluation of clinical features .......................................................................... 33 Evaluation of morphological variants ............................................................... 35 Immunohistochemistry ................................................................................... 36 Genetic studies ............................................................................................... 37 Cytogenetic analysis ......................................................................... 37 Fluorescence in situ hybridisation ......................................................... 37 Southern blot hybridisation ................................................................. 37 Comparative genomic hybridisation ....................................................... 37 Loss of heterozygosity analysis ............................................................ 38 Treatment of lymphoma .................................................................................. 38