LARGE-CELL VARIANTS OF MANTLE CELL LYMPHOMA - CYTOLOGIC CHARACTERISTICS AND P53 ANOMALIES MAY PREDICT POOR OUTCOME

Large-cell variants are uncommon in mantle cell lymphoma (MCL), Here w e describe the pathologic and clinical findings in five patients with large-cell lymphoma related to MCL (L-MCL), and compare them to a grou p of classic small-cell MCL (s-MCL) cases, Histologically, the MC orig in of the large cells was evinced by their association with a small ma ntle cell component in the same tissue, or their distribution in a cla ssic mantle zone pattern, or their development in a patient with previ ous s-MCL. The large cells were either pleomorphic mantle cells (case 1) or transformed blast-like cells (cases 2-5). The median nuclear dia meter, median nuclear area and proliferation index of L-MCLs and s-MCL s, were statistically different. Immunophenotypic characterization of four specimens of L-MCL and 10 of s-MCLs with a large panel of antibod ies showed the classic findings of MCL, i.e. the IgM(+) D-+/-, CD5(+), CD10(-), CD23(-) phenotype in all cases except two (one CD5(-) and on e CD23(+)), and the association with a loose follicular dendritic cell network. Two of four L-MCLs and 5/10 s-MCLs demonstrated rearrangemen ts of the bcl-1 gene by Southern blot or by polymerase chain reaction (PCR); 2/4 L-MCLs and 1/9 s-MCLs had p53 mutations on single-strand co nformation polymorphism analysis; none of the 14 specimens showed rear rangement of bcl-2 by PCR or bcl-6 and c-myc by Southern blot, All pat ients with 'transformed' histology (versus 37% of all others)died of l ymphoma; their survival (15-18 months: median 17) was much shorter tha n that of all the others (28-117+ months; median 43) (P=0.0035). All t hree patients with p53 anomalies, two of whom had tumours with transfo rmed histology, died of their disease in a short time (15, 18 and 28 m onths). In contrast, the presence of bcl-1 rearrangements did not have prognostic implications. ' This study documents the existence of larg e-cell variants of MCL and the poor prognosis associated with the 'tra nsformed' cytologic type and/or p53 abnormalities.