BCL2 gene abnormalities define distinct clinical subsets of follicular lymphoma

Aims:  Follicular lymphoma (FL) arising primarily in the skin has recently been proposed as a distinct entity on the basis of a low incidence of t(14;18)(q32;q21) and bcl-2 expression, with a very high percentage of patients surviving more than 5 years. However, cases of t(14;18)(q32;q21)-positive primary cutaneous FL (PCFL) and examples of t(14;18)(q32;q21)-negative FL at nodal and other extranodal sites, are well documented. The aim of this study was to test the hypothesis that there is a subtype of FL lacking t(14;18)(q32;q21), which preferentially involves certain sites but is not restricted by anatomical location. Methods and results:  A cohort of 47 stage 1 FL was stratified according to the presence or absence of t(14;18)(q32;q21) using conventional cytogenetics, polymerase chain reaction and interphase fluorescence in situ hybridization. Compared with t(14;18)(q32;q21)-positive cases, FL lacking the translocation were less likely to express CD10 or bcl-2 (P < 0.01), made up a significantly greater proportion of cases arising at extranodal sites (P < 0.001) and had a significantly better overall and disease-specific 5-year survival (P < 0.01). Conclusions:  These results support the concept of a subtype of FL lacking t(14;18)(q32;q21), characterized by low-intensity bcl-2 expression, a predilection for extranodal sites, particularly the skin, and a more favourable outcome than t(14;18)(q32;q21)-positive FL.