Differentiating between leukaemic presentation of B cell non-Hodgkin lymphomas and chronic B cell leukaemias based on morphological and immunophenotyping studies alone can be very difficult. The World Health Organisation recognises that genetic abnormalities are one of the most reliable criteria for the classification of malignant lymphomas.1
Although t(11;14)(q13;q32) or its molecular counterpart, CCND1 rearrangement, can be detected using various methods such as conventional cytogenetics, Southern blot, and PCR analysis, the FISH technique has proved to be a highly sensitive tool for the detection of the t(11;14) translocation, irrespective of the localisation of the breakpoints in the CCND1 gene or the presence of cycling cells.2–4
In our present case, chromosomes 11 and 14 were normal by standard cytogenetics. However, metaphase and interphase FISH analysis showed the occurrence of a microinsertion of the CCND1 gene into the IgH locus, leading to overexpression of cyclin D1 in lymphoid bone marrow cells. The hybridisation pattern in interphase cells in our patient was identical to that described in cases with t(11;14)(q13;q32) associated with a deletion involving the variable region of IgH.2
Therefore, additional conventional cytogenetic studies are advisable in cases with this interphase FISH pattern to rule out this microinsertion not previously described in mantle cell lymphoma.
“The fluorescence in situ hybridisation technique has proved to be a highly sensitive tool for the detection of the t(11;14) translocation, irrespective of the localisation of the breakpoints in the CCND1 gene”
Similar submicroscopic insertions have been reported in other cytogenetic–clinicopathological entities, such as chronic and acute myeloid leukaemias in which fusion genes are generated without morphologically altering the chromosomes.5,6
Moreover, insertional events arising during aberrant immunoglobulin switch recombination have been described in a myeloma tumour cell line in which an IgH sequence containing the 3′ IgH enhancer was inserted into chromosome 11, resulting in overexpression of cyclin D1.7
In addition, an insertion of 132 bp of chromosome 22q12 sequence into the 5′ region flanking Sμ on chromosome 14q32 has been reported in a patient with multiple myeloma.8
With regard to secondary chromosomal abnormalities, the most frequent rearrangements described in mantle lymphoma are genomic imbalances, which appear to indicate poor prognosis.9,10
In our patient, no chromosomal imbalance was detected by interphase cytogenetics for del17p53, del13q14, and trisomy 12 or by comparative genomic hybridisation analysis (data not shown). Given the indolent clinical course in our patient, presenting features such as morphological small cell type, non-nodal disease, and no chromosomal imbalances may be of clinical interest in the management of patients with mantle cell lymphoma.
Take home messages
- Leukaemic mantle cell lymphoma is characterised by the t(11;14)(q13;q32) translocation, in which the CCDN1 gene locus is juxtaposed with the immunoglobulin heavy chain (IgH) gene locus, resulting in overexpression of the cyclin D1 protein
- We describe a unique case of leukaemic mantle cell lymphoma with a submicroscopic insertion of the CCDN1 gene at the IgH locus, producing a hybridisation fusion signal on an apparently normal chromosome 14 and overexpressing cyclin D1 on bone marrow cells