Rearrangements of MALT1, IgH, FOXP1, BCL3 and PAX5 Are Rare Events in Extranodal Marginal Zone Lymphoma in the UK.
Authors: Barrans Sharon L. , Turner Kathryn , O’Connor Sheila J.M. , Jack Andrew S. , Owen Roger G. 
Published: April 2020

A number of balanced translocations have been described in extranodal marginal zone lymphoma (ENMZL). The t(11;18) and variant t(14;18) which deregulate MALT1 are the commonest reported occurring in up to 40% of patients. The t(3;14) which deregulates FOXP1 is reported to occur in up to 10% of cases whilst the t(1;14) and t(14;19) which deregulate BCL10 and BCL3 respectively have been described in a variable proportion of patients. The purpose of this study was to evaluate the incidence of such abnormalities in the routine diagnostic setting in a geographically defined region of Northern England. We have therefore reviewed a series of 56 consecutive cases of presenting ENMZL, diagnosed between November 2003 and July 2006 in the Yorkshire and Humberside Haematology Network (YHHN), which serves a population of approximately 3.6 million. Diagnoses were made using WHO criteria. Presentation tissue included breast (2), gastric (29), colon (3), Conjuctiva/orbit (3), connective tissue/muscle (3), lung (2), parotid (2), salivary gland (2), thyroid (1), prostate (2), and skin (4). In 2 cases the site was unknown. All cases were investigated for MALT1 rearrangements with an alpha satellite 18 control (VYSIS 32-190055/D18Z1) using interphase FISH at the time of diagnosis. Cases with available biopsy material were further investigated for rearrangements of IgH, (VYSIS 32-191019), PAX5, BCL3 (DAKO Y5413 and Y5411) and FOXP1 (in-house probe). FISH was perormed on thin paraffin sections in 54/56 cases and on fresh tissue imprints in 2 cases. 6/56 (11%) cases demonstrated a rearrangement of MALT1, 5/6 were of gastric origin and 1 colonic. 16/56 (29%) cases demonstrated trisomy 18. 6/44 (14%) cases showed rearrangement of IgH (3/6 were unbalanced rearrangement with loss). In 1 of these cases (gastric) BCL3 was also rearranged, suggesting that this may represent a t(14;19)(q32;q13). 1 additional case (parotid) showed an unbalanced rearrangement of BCL3 with loss of the telomeric portion of the gene, giving a total of 2/30 (7%) cases with BCL3 abberrations. In the latter case no other abnormalities were demonstrated. A further 5 cases were suspicious for IgH rearrangements with a low level of cells (&lt;10%) showing rearrangement. No cases were demonstrated to have rearrangement of PAX5 or FOXP1, but 6/32 (19%) cases showed 3 copies of PAX5 and similarly 7/30 (23%) had extra copies of FOXP1, consistent with complete or partial trisomy of chromosomes 9 and 3.

The incidence of MALT1 rearrangements in this study is significicantly lower than most published series. The reasons for this apparrent discrepancy is unclear at present but this study represents a consecutive series of patients presenting in a defined UK cancer network and is therefore free from any referral bias. We similarly failed to demonstrate rearrangements of either FOXp1 or PAX5. Rearrangement of BCL3 was however demonstrated but at low frequency. It is clear that although significant advances have been made in our understanding of the pathobiology of ENMZL the underlying cytogenetic defect remains unknown in the majority of patients.