Monoclonal B cell lymphocytosis and "in situ" lymphoma

The finding of monoclonal B-cell populations not fulfilling criteria for a lymphoid malignancy has given great impulse to study mechanisms involved in lymphomagenesis and factors responsible for the transition from B-cell precursor states to overt lymphoproliferative disorders. Monoclonal B cell expansions were initially recognized in peripheral blood of otherwise healthy subjects (thus defined monoclonal B-cell lymphocytosis, MBL) and in most cases share the immunophenotypic profile of chronic lymphocytic leukemia (CLL). The clinical relevance of this phenomenon is different according to B-cell count: high-count MBL is considered a preneoplastic condition and progresses to CLL requiring treatment at a rate of 1-2% per year, while low-count MBL, though persisting over time, has not shown a clinical correlation with frank leukemia so far. MBL other than CLL-like represent a minority of cases and are ill-defined entities for which clinical and biological information is still scanty. In situ follicular lymphoma (FL) and mantle cell lymphoma (MCL) are characterized by the localization of atypical lymphoid cells, carrying t(14;18)(q32;q21) or t(11;14)(q13;q32), only in the germinal centers and mantle zones respectively, where their normal counterparts are localized. The localization of these cells indicates that germinal centers or mantle zones provide appropriate microenvironments for cells carrying these oncogenic alterations to survive or proliferate. The progression of these lesions to overt lymphomas occurs rarely and may require the accumulation of additional genetic events. Individuals with these lymphoid proliferations should be managed with caution.