Cytogenetics

Abstract

The various histopathologic subtypes of mature lymphoid malignancies have very different natural courses and show variable responses to therapy; modern treatment depends on accurate classification of lymphomas, and the patterns of both primary and secondary chromosomal abnormalities are often a key component of the classification (Swerdlow SH, Campo E, Harris NL et al, WHO classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, 2008). Although the identification of chromosomal aberrations in a suspected mature lymphoid neoplasm frequently provides essential information for establishing a precise and accurate diagnosis, there are relatively few cytogenetic abnormalities that are highly specific for particular histopathologic subtypes of lymphoma (Heim S, Mitelman F, Cancer cytogenetics. Wiley, Hoboken, 2009; Dave BJ, Nelson M, Sanger WG, Clin Lab Med 31:725-761, 2011; Kluin P, Schuuring E, Histopathology 58:128-144, 2011). The results of cytogenetic analysis, therefore, must be incorporated into the multidisciplinary diagnostic workup for mature lymphoid tumors, which includes histopathologic features, immunophenotype, clinical presentation, and the results of other genetic testing. With the advent of fluorescence in situ hybridization (FISH) technologies and their implementation in paraffin-embedded tissues, it is now more feasible to identify specific diagnostically and prognostically important genetic alterations in defined chromosomal regions (Dave BJ, Nelson M, Pickering DL et al, Cancer Genet Cytogenet 132:125-132, 2002). In the near future, cytogenetic data will need to be integrated into even more complex diagnostic processes, which will include findings from array-based technologies (such as gene expression profiling, or array CGH and SNP array testing) and extensive mutation testing. This chapter reviews the seminal cytogenetic and molecular cytogenetic alterations as they present in the different subtypes of rare lymphomas, and the optimal approaches to detect these abnormalities in lymphoid malignancies, including the mature B-cell and T-cell neoplasms and Hodgkin lymphoma (HL).