Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression.

AIMS: The variable morphology of mantle cell lymphoma (MCL) is assumed to reflect progression from an early form with classical cytology and mantle zone or nodular growth to a later, more aggressive variant of the disease with blastoid cytology and a diffuse growth pattern. However, studies of sequential biopsies of MCL are very limited, and we therefore undertook to carry out such a study. METHODS AND RESULTS: We analysed a cohort of 47 MCLs at primary diagnosis and relapse for cytology, growth pattern, and Ki67 index, and correlated the findings with outcome. In the majority of cases, the mantle zone growth pattern was lost, but it had been reacquired in a small subset of MCLs at relapse. Twenty-two per cent of MCLs with classical/small cell cytology acquired blastoid features during the course of the disease. However, 50% of MCLs with blastoid cytology at primary diagnosis recurred as a classical variant. The Ki67 index increased over time, and was associated with prognosis in the primary and the relapse biopsy specimens. CONCLUSIONS: This is the first study to show, in a large cohort of MCLs, that the Ki67 index increases over time in MCL. Assessment of the Ki67 index remains a useful prognostic tool if assessment is performed in the relapse situation.