Classical and molecular methods in differentiation of mantle cell lymphoma and small lymphocytic lymphoma in composite lymphoma: a case report

Abstract

Composite lymphoma (CL) is a very rare phenomenon. To date, only few cases of composite mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have been reported by Sun et al. (Cytometry B Clin Cytom 2018;94(1):148-50), Hoeller et al. (Hum Pathol 2013;44(1):110-21), and Papathomas et al. (Hum Pathol 2012;43(4):467-80). In the majority of CL cases, the clonality relationship was not examined or could not be proven. So far, there is no optimal treatment strategy for CL. However, it has been a commonly accepted rule that the more aggressive component should be treated first. Thus, it is of vital importance to precisely distinguish the components of CL and to determine the response of a particular component to treatment. This may be done by monitoring the molecular minimal residual disease (mMRD) as reported by Pott et al. (Blood 2010;115(16):3215-23) and Pott (Semin Hematol 2011;48(3):172-84). This report presents the possibility of determining clonality of each CL component by using flow cytometry in parallel with specific molecular markers. Molecular analysis was performed by quantitative real-time PCR (qPCR) using two markers: IGH rearrangement as reported by van Dongen et al. (Leukemia 2003;17(12):2257-317) and SOX11 expression by Hamborg et al. (Eur J Haematol 2012;89(5):385-94) and Szostakowska et al. (Med Oncol 2018;35(4):49). The SOX11 expression allowed us to distinguish MCL and SLL subclones in a 60-year-old male with multifocal MCL/SLL as this marker is not detected in SLL as reported by Swerdlow et al. (2001) and Mozos et al. (Haematologica 2009;94(11):1555-62). To our best knowledge, this is the first example of the use of mMRD to distinguish CL components.